Using Diet to Optimize Circulating Biomarkers: Serum Bicarbonate

In an earlier post, I wrote about the association between biomarkers of systemic acid-base balance (serum bicarbonate, the anion gap, urinary pH) with all-cause mortality risk (https://michaellustgarten.com/2015/08/28/serum-bicarbonate-and-anion-gap-whats-optimal/). Based on these data, systemic acidity may not be optimal for health and longevity, when compared with more alkaline values. Can circulating acid-base biomarkers be optimized through diet?

One way to optimize serum bicarbonate is with a low dietary PRAL (potential renal acid load). For a given food, PRAL is a measure of how much acid or base that the kidney will see. In subjects with normal kidney function (or with chronic kidney disease, CKD), a low dietary PRAL (alkaline-forming) is associated with high serum bicarbonate, whereas a high dietary PRAL (acid-forming) is associated with reduced serum bicarbonate (Ikizler et al. 2015):

bicarb pral

So how can we achieve a low dietary acid intake (low PRAL), with the goal of increasing serum bicarbonate? The answer is to abundantly consume foods with a low PRAL (vegetables), while minimizing foods with a high PRAL (animal products, grains). Let’s have a look at the PRAL values for several food groups (Remer and Manz, 1995):

All of the meat and meat products shown below have acid-forming, positive PRAL values:

PRAL meat

Similarly, fish have acid-forming, positive PRAL values:

fish pral

While PRAL values for milk, dairy, and eggs are generally acid-forming, there is a wider range, compared with meat and fish. For example, parmesan and cheddar cheese have high PRAL values (34.2, 26.5, respectively), whereas milk and yogurt have PRAL values ~1:

dairy pral

Grains are similar to animal products in terms of their PRAL values:

grain pral

In contrast, all of the vegetables on the list below have very low, alkaline-forming PRAL values. The All-Star for a low PRAL is spinach (-14):
veg pral

Similarly, most fruits have alkaline forming, low PRAL values. Although raisins seem to be the PRAL All-Star, their data (and all of the other foods on the list) are based on 100g (299 calories for raisins). For an equivalent amount of calories for strawberries, their PRAL equates to -20.6, which is similar to the raisin PRAL. Also included on the list are nuts, which contain a range of PRAL values from negative (hazelnuts) to positive (walnuts, peanuts):

fruit pral

What’s my dietary PRAL? To determine that, it’s first important to define the PRAL equation: PRAL = (0.49 * protein intake in g/day) + (0.037 * phosphorus intake in mg/day) – (0.02 * potassium intake in mg/day) – (0.013 * calcium intake in mg/day) – (0.027 * magnesium intake in mg/day; Remer and Manz, 1994). Using my latest 7-day average dietary data yields a very low, alkaline-forming PRAL, -121.9: (protein, 88g; phosphorus, 2038 mg; potassium, 9868 mg; calcium, 1421 mg; magnesium, 901 mg)! It’s important to note that the major contributor to my very low PRAL value comes from the potassium term. Because of my abundant vegetable intake, my potassium intake is very high, resulting in a highly alkaline PRAL. Considering that PRAL values of -40 were associated with serum bicarbonate values of ~28, my serum bicarbonate value of 31 on my last blood test (8/2015) may in part be explained by my very low dietary PRAL value, -121.9.

Another measure of dietary acid load is NEAP (net endogenous acid production). In subjects with normal (and reduced, CKD) kidney function, a high NEAP diet (acid-forming) is associated with reduced serum bicarbonate, whereas a low NEAP diet (alkaline-forming) is associated with higher serum bicarbonate values (Ikizler et al. 2015):

neap bicarb

NEAP is more easily calculated than PRAL-all you need to know are your dietary protein and potassium intakes: NEAP = (54.5 * protein intake in grams/day)/(potassium intake in mEq/day) -10.2 (Frassetto et al. 1999). To convert your daily potassium intake from mg to mEq, divide by 39.1. Using my 7-day average protein and potassium intake data yields a NEAP = (54.5 * 88)/(9868/39.1) – 10.2 = 8.8. Based on the plot above for NEAP vs. serum bicarbonate, that again puts me on the far left, which is associated with serum bicarbonate values greater than 28.

Collectively, eating more potassium-rich vegetables will reduce PRAL and NEAP, which is associated with systemic alkalinity, as measured by an elevated serum bicarbonate. Because high serum bicarbonate levels are associated with reduced all-cause mortality risk, this may be an important strategy for improving health and longevity!

If you’re interested, please have a look at my book!

References

Frassetto LA, Todd KM, Morris RJC, Sebastian A. Estimation of net endogenous noncarbonic acid production in humans from diet potassium and protein contents. Am J Clin Nutr. 1998;68:576-583.

Ikizler HO, Zelnick L, Ruzinski J, Curtin L, Utzschneider KM, Kestenbaum B, Himmelfarb J, de Boer IH. Dietary Acid Load Is Associated With Serum Bicarbonate but not Insulin Sensitivity in Chronic Kidney Disease. J Ren Nutr. 2016 Mar;26(2):93-102.

Remer T, Manz F. Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein. Am J Clin Nutr. 1994;59:1356-1361.

Remer, T. and Manz, F. Potential renal acid load of foods and its influence on urine pH. Journal of the American Dietetic Association 1995 ;95(7), 791-797.

Total Cholesterol: What’s Optimal For Longevity?

On my latest blood test (August 2015), my total cholesterol was 127 mg/dL-is that value optimal for health and longevity?

Based on data for 1,104,294 men younger than 60y (median age, 40y) that were followed for up to 14 years (Fulks et al. 2009), my 127 mg/dL value (1 – 2.4%) puts me relatively close to maximally reduced all-cause mortality risk, which occurs at 146-158 mg/dL (5-9% on the graph below):

c hdl mort

But what about the data for men older than 60?

In a 10-year study of 2,277 older adults (average age, ~77y), total cholesterol levels less than 175 mg/dL were associated with ~2-fold higher risk of all-cause mortality, compared with values greater than 226 mg/dL (Schupf et al. 2005):

tc less 175 acm

Similarly, in a 10-year study of even older adults (median age, 89y; 724 subjects), all-cause mortality risk was significantly increased in subjects with total cholesterol values less than 193 mg/dL (dark black line below), compared with values greater than 251 mg/dL (dashed line; Weverling-Rijnsburger et al. 1997). In addition, subjects with cholesterol values greater than 251 mg/dL lived ~2 years longer than those with values less than 191 mg/dL. So higher cholesterol in very old adults…increased lifespan! Does that mean I should alter my dietary approach to increase my circulating cholesterol levels after I reach 60?

chol 89y mort.png

To address that issue, it’s important to understand why cholesterol increases during aging. One possible mechanism involves the role of cholesterol in immune defense against infectious agents (bacteria, viruses, parasites, etc.). Obviously, our immune system is supposed to eliminate these pathogens, but immune function decreases with age (Targonski et al. 2007). As a compensatory mechanism, cholesterol can protect against infectious agents. For example, LDL cholesterol binds to and partially inactivates Staphylococcus aureus (Bhakdi et al. 1983). Staphylococcus aureus infection increases during aging, as its incidence rate is ~3-fold higher in adults older than 60y, when compared with younger subjects (Laupland et al. 2008). In addition, LDL cholesterol inhibits bacterial endotoxin (Weinstock et al. 1992), whose presence in the blood increases during aging (Ghosh et al. 2015). In support of the link between circulating cholesterol with infectious agents, in the older adults of Weverling-Rijnsburger et al. (1997), cholesterol values greater than 251 mg/dL (solid black line) were associated with significantly decreased infectious disease-related mortality, when compared with values less than 193 mg/dL:

infect mort

So if we’re better able to keep infectious agents out of our blood, that would be expected to reduce the need for elevated circulating cholesterol during aging. How can we do that?

One approach involves increased dietary fiber. Fermentation of dietary fiber by gut bacteria produces short-chain fatty acids, which improve gut barrier function (Chen et al. 2013), and decrease cholesterol synthesis (Wright et al. 1990). However, older adults do not eat high-fiber diets, as values of only ~19g/day have been reported (Lustgarten et al. 2014). In contrast, dietary fiber intakes greater than only 29g/day are associated with less infectious disease (and all-cause mortality) risk (Park et al. 2011). So definitely eating at least 29g fiber/day is important, but is that amount optimal to minimize the need for elevated cholesterol during aging?

In a 2-week study of the role of dietary fiber on circulating cholesterol, subjects that ate only 10g fiber/1000 calories did not significantly reduce their baseline total cholesterol values from ~182 mg/dL (Jenkins et al. 2001). In contrast, a dietary fiber intake of 19g/1000 calories reduced baseline total cholesterol from 185 to 150 mg/dL, and subjects that ate even more fiber than that, 55g/1000 calories reduced their total cholesterol values from ~182 to 142 mg/dL, a drop that was also significantly different compared with the 19g fiber/1000 calorie group.

Collectively, these data suggest that to maximally boost gut barrier function, thereby minimizing circulating infectious agents and the need for elevated circulating cholesterol during aging, a very-high fiber-diet may be important. Accordingly, my average daily fiber intake is ~100 g/day on a 2300 calorie diet, resulting in ~43g fiber/1000 calories. Based on this, I don’t expect for my total cholesterol values to change during aging, as my gut barrier function will be optimal, and infectious agents in my blood will be minimized.

To add some specificity to this approach, 2 additional measurements may be important: serum albumin and HDL cholesterol. In agreement with the studies of Weverling-Rijnsburger et al. and Schupf et al., in a 5-year study of 4,128 older adults (average age, ~79y), those with total cholesterol values less than 160 mg/dL had significantly higher all-cause mortality risk, compared with values greater than 240 mg/dL (Volpato et al. 2001):

low tc mortl

However, when considering subjects’ albumin and HDL cholesterol levels, the differential mortality risk was abolished. Subjects that had low total cholesterol but also high (within-range) albumin and HDL had improved survival compared to the higher cholesterol groups:

adj tc mort for alb hdl

If your total cholesterol values are less than 160 mg/dL, what serum albumin and HDL values should you shoot for? As shown below, albumin levels greater than 38 g/L and HDL values greater than 47 mg/dL were associated with maximally reduced all-cause mortality risk in subjects with total cholesterol values less than 160 mg/dL (Volpato et al. 2001):

volpato

My albumin values are consistently between 46-48 g/L, but during recent measurements my HDL levels have been lower than optimal (35 mg/dL on 8/2015). The good news is that I was able to increase my HDL from 28 (7/2013 measurement) to 35 mg/dL by adding ~4 oz of fish every day! To further increase my HDL, I’ve doubled my fish oil intake (~3.3 g of combined EPA + DHA per day, from 5-9 g of cod liver oil). I’ll test the effect of this on my circulating biomarkers in a couple of months, so stay tuned!

3/23/2016 Update: Because of concerns that the pre-formed Vitamin A (that is found in cod liver oil) may negate the potential health-promoting effects of optimal Vitamin D levels (Schmutz et al. 2016), I stopped taking cod liver oil during the 3-month period that preceded my latest blood test (3/23/2016). However, I was able to increase my HDL from 35 to 53 mg/dL! I attribute this increase to the daily inclusion of ~60g/walnuts per day. In doing that, although I only replaced ~200 calories from carbohydrates with fat, lower carbohydrate diets have been shown to increase HDL (Manor et al. 2016).

Nonetheless, in terms of the all-cause mortality data that includes total cholesterol (137 mg/dL), albumin (51 g/L), and HDL (53 mg/dL), based on my latest blood test results, my risk is now maximally low!

If you’re interested, please have a look at my book!

References

Bhakdi S, Tranum-Jensen J, Utermann G, Füssle R. Binding and partial inactivation of Staphylococcus aureus alpha-toxin by human plasma low density lipoprotein. J Biol Chem. 1983 May 10;258(9):5899-904.

Chen H, Mao X, He J, Yu B, Huang Z, Yu J, Zheng P, Chen D. Dietary fibre affects intestinal mucosal barrier function and regulates intestinal bacteria in weaning piglets. Br J Nutr. 2013 Nov;110(10):1837-48.

Eaton SB, Eaton SB 3rd, Konner MJ. Paleolithic nutrition revisited: A twelve-year retrospective on its nature and implications. Eur J Clin Nutr. 1997 Apr;51(4):207-16.

Fulks M, Stout RL, Dolan VF. Association of cholesterol, LDL, HDL, cholesterol/ HDL and triglyceride with all-cause mortality in life insurance applicants. J Insur Med. 2009;41(4):244-53.

Ghosh S, Lertwattanarak R, Garduño Jde J, Galeana JJ, Li J, Zamarripa F, Lancaster JL, Mohan S, Hussey S, Musi N. Elevated muscle TLR4 expression and metabolic endotoxemia in human agingJ Gerontol A Biol Sci Med Sci. 2015 Feb;70(2):232-46.

Jenkins DJ, Kendall CW, Popovich DG, Vidgen E, Mehling CC, Vuksan V, Ransom TP, Rao AV, Rosenberg-Zand R, Tariq N, Corey P, Jones PJ, Raeini M, Story JA, Furumoto EJ, Illingworth DR, Pappu AS, Connelly PW. Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and colonic function. Metabolism. 2001 Apr;50(4):494-503.

Laupland KBRoss TGregson DBStaphylococcus aureus bloodstream infections: risk factors, outcomes, and the influence of methicillin resistance in Calgary, Canada, 2000-2006. J Infect Dis. 2008 Aug 1;198(3):336-43.

Lustgarten MS, Price LL, Chalé A, Fielding RA. Metabolites related to gut bacterial metabolism, peroxisome proliferator-activated receptor-alpha activation, and insulin sensitivity are associated with physical function in functionally-limited older adults. Aging Cell. 2014 Oct;13(5):918-25.

Mansoor N, Vinknes KJ, Veierød MB, Retterstøl K. Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials. Br J Nutr. 2016 Feb;115(3):466-79.

Park Y, Subar AF, Hollenbeck A, Schatzkin A. Dietary fiber intake and mortality in the NIH-AARP diet and health study. Arch Intern Med. 2011 Jun 27;171(12):1061-8.

Schmutz EA, Zimmermann MB, Rohrmann S. The inverse association between serum 25-hydroxyvitamin D and mortality may be modified by vitamin A status and use of vitamin A supplements. Eur J Nutr. 2016 Feb;55(1):393-402.

Schupf N, Costa R, Luchsinger J, Tang MX, Lee JH, Mayeux R. Relationship Between Plasma Lipids and All-Cause Mortality in Nondemented Elderly. J Am Geriatr Soc. 2005 Feb;53(2):219-26.

Targonski PV, Jacobson RM, Poland GA. Immunosenescence: role and measurement in influenza vaccine response among the elderly. Vaccine. 2007 Apr 20;25(16):3066-9.

Vasto S, Scapagnini G, Rizzo C, Monastero R, Marchese A, Caruso C. Mediterranean diet and longevity in Sicily: survey in a Sicani Mountains population. Rejuvenation Res. 2012 Apr;15(2):184-8.

Volpato S, Leveille SG, Corti MC, Harris TB, Guralnik JM. The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterolJ Am Geriatr Soc. 2001 Sep;49(9):1142-7.

Weinstock C, Ullrich H, Hohe R, Berg A, Baumstark MW, Frey I, Northoff H, Flegel WA. Low density lipoproteins inhibit endotoxin activation of monocytes. Arterioscler Thromb. 1992 Mar;12(3):341-7.

Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RG. Total cholesterol and risk of mortality in the oldest old. Lancet. 1997 Oct 18;350(9085):1119-23.

Wright RS, Anderson JW, Bridges SR. Propionate inhibits hepatocyte lipid synthesis. Proc Soc Exp Biol Med. 1990 Oct;195(1):26-9.

The Essential Fatty Acid, Linoleic Acid: Dietary Intake And Circulating Values, What’s Optimal For Health?

Linoleic acid (C18:2, n-6) is an essential fatty acid that must be obtained from the diet, because  our body can’t make it. How much linoleic acid should we eat every day for optimal health? To answer this question, I’ll investigate the association between circulating levels of linoleic acid with all-cause mortality risk, followed by identification of a corresponding dietary intake. Let’s have a look!

First, are circulating levels of linoleic acid associated with all-cause mortality risk? 4 studies have investigated this issue:

  • In a 15-year study of 1,551 middle-aged men (average age, 52y), increased circulating linoleic acid was associated with significantly reduced all-cause mortality risk in 3 of the 4 multivariable-adjusted models (Laaksonen et al. 2005).
  • In a 15-year study of 4,232 older adults (60y) elevated circulating linoleic acid was associated with significantly reduced all-cause mortality risk in men, but not women (Marklund et al. 2015).
  • In a 34-year study of 2,009 middle-aged men (average age, 50y) increased circulating linoleic acid was associated with significantly decreased risk of all-cause mortality (Warensjö et al. 2008). For example, shown below is the association between the risk of death from cardiovascular-related disease with the circulating linoleic acid concentration. At both 20 and 30 years after study onset, subjects that had circulating linoleic values above the median had approximately half of the mortality risk from CVD, when compared with below-median values for linoleic acid.

LA CVD mortality

  • In a 13-year study that included both older men and women (average age, 74y), and, more subjects (2,792) than the studies of Laaksonen and Warensjöet combined, plasma phospholipid percentages of linoleic acid greater than ~21-24% were associated with significantly reduced all-cause mortality risk:

LA total mort

Colectively, these 4 studies show that increased circulating levels of linoleic acid are associated with reduced all-cause mortality risk. How much linoleic acid should we eat to achieve optimal circulating values? In other words, what dietary intake of linoleic acid corresponds to 21%+ of plasma phospholipid linoleic acid? Based on the data below, dietary intakes of linoleic acid that are greater than 14% of total calories are associated with circulating linoleic acid values of 21% (Wu et al. 2014).

LA dietary in PL

On my ~2300 calorie diet, that translates into 322 calories (36g) from linoleic acid. I get a significant amount of dietary linoleic acid from one of the best linoleic acid food sources, walnuts, which contain 5.8 grams of linoleic acid per 100 calories (see Lipids, C18:2, http://ndb.nal.usda.gov/ndb/foods/show/3690?fg=&man=&lfacet=&count=&max=&qlookup=&offset=&sort=&format=Full&reportfmt=other&rptfrm=&ndbno=&nutrient1=&nutrient2=&nutrient3=&subset=&totCount=&measureby=&_action_show=Apply+Changes&Qv=.152&Q6919=1&Q6920=1&Q6921=1&Q6922=1&Q6923=1&Q6924=1).

Just using walnuts alone, I’d need ~700 calories per day to reach 14% dietary linoleic acid! Although I’m always interested in dietary strategies that may reduce all-cause mortality risk, allocating ~30% of my daily calories to only walnuts is not ideal for my high-fiber approach to health (https://michaellustgarten.com/2015/07/17/on-a-paleo-diet-not-if-you-fiber-intake-is-less-than/), nor would it satiate me, as high-volume vegetable meals are best for that. A more reasonable dietary linoleic acid target (for now) is ~8%, the point at which plasma linoleic acid mostly plateaus (see the plot above). 8% on my 2300 calorie diet translates into 20 grams of linoleic acid per day. I should note that I also get a good amount of linoleic acid (6.4 grams) from the 30 grams of sesame seeds that goes into my giant salad’s dressing, which I eat 2-3x per week. When combined with ~300 calories from walnuts/day, that gets me to at least 8% of my daily calories from linoleic acid.

If you’re interested, please have a look at my book!

References:

Laaksonen DE, Nyyssönen K, Niskanen L, Rissanen TH, Salonen JT. Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids. Arch Intern Med. 2005 Jan 24;165(2):193-9.

Marklund M, Leander K, Vikström M, Laguzzi F, Gigante B, Sjögren P, Cederholm T, de Faire U, Hellénius ML, Risérus U. Polyunsaturated Fat Intake Estimated by Circulating Biomarkers and Risk of Cardiovascular Disease and All-Cause Mortality in a Population-Based Cohort of 60-Year-Old Men and Women. Circulationz 2015 Aug 18;132(7):586-94.

Warensjö E, Sundström J, Vessby B, Cederholm T, Risérus U. Markers of dietary fat quality and fatty acid desaturation as predictors of total and cardiovascular mortality: a population-based prospective study. Am J Clin Nutr. 2008 Jul;88(1):203-9.

Wu JH, Lemaitre RN, King IB, Song X, Psaty BM, Siscovick DS, Mozaffarian D. Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the CardiovascularHealth StudyCirculation. 2014 Oct 7;130(15):1245-53

Vitamin C: Dietary Intake And Plasma Values, What’s Optimal For Health?

How much Vitamin C (ascorbic acid) is optimal for health? To answer this question, I’ll examine the association between circulating levels of Vitamin C with all-cause mortality risk. Then, which dietary Vitamin C intake corresponds to optimal plasma levels? Let’s have a look!

A variety of studies have investigated associations between plasma (or serum) Vitamin C with all-cause mortality risk:

  • In a 4-year study of 1,115 older adults (average age ~79y), plasma vitamin C values greater than 66 uM (micromolar) were associated with significantly decreased all-cause mortality risk, when compared with values less than 17 uM (Fletcher et al. 2003).
  • In a 12-year study of 725 older adults (average age, 73y), plasma vitamin C values greater than 52 uM were associated with significantly reduced all-cause mortality risk (Sahyoun et al. 1996). Interestingly, the most reduced mortality risk was found in those with plasma Vitamin C values greater than 89 uM, a value that can only be attained with dietary Vitamin C intakes greater than 1000 mg/day (more on this below!).
  • In a 16-year study of 8,453 middle-aged adults (average age ~49y), serum Vitamin C values greater than 45 uM were associated with significantly reduced all-cause mortality risk, when compared with values less than 17 uM (Simon et al. 2001).
  • In a 13-year study of 948 older adults (average age, 67y), serum Vitamin C values greater than 55 uM were associated with significantly reduced all-cause mortality risk, when compared with values less than 13.5 uM (Wang et al. 2018).
  • In a 13-year study of 1,054 older adults (average age ~76y), elevated plasma levels of Vitamin C (risk ratios were reported without the actual Vitamin C concentration) were associated with significantly decreased all-cause mortality risk (Bates et al. 2011).
  • In a 4-year study of 19,496 older adults (average age ~59y), plasma Vitamin C values greater than 48 uM in men and 59 uM in women (both in quintile 3, shown below) were associated with significantly reduced all-cause mortality risk (Khaw et al. 2001). The most reduced all-cause mortality risk included average Vitamin C values of 73 uM for men and 85 uM for women (shown below in quintile 5), values which require greater than 500 mg of dietary Vitamin C/day (more on this also below!).

C risk

Studies that show weaker or no association between the plasma Vitamin C concentration with all-cause mortality risk include Loria et al. (2000) and Jia et al. (2007). In Loria et al. (2000), 9,450 middle aged adults (~48y) were followed for 12-16 years. Men in the highest Vitamin C quartile (> 74 uM) had significantly reduced all-cause mortality risk, when compared with men in the low plasma Vitamin C group (< 28 uM). Although a similar association was identified for women, significance was lost after multivariable adjustment. In Jia et al. (2007), although plasma Vitamin C values less than 61 uM were associated with increased all-cause mortality risk in older adults (median age, ~80y) that were studied for ~7.5 years, these data were not statistically significant (p-value = 0.18). However, the study sample size (398 subjects) may have been too small to detect significant effects.

Collectively these studies show that low circulating levels of Vitamin C may be related to increased mortality risk, whereas plasma values greater than ~50 uM are consistently associated with reduced all-cause mortality risk. How much dietary vitamin C is required to attain 50 uM+?

As shown below, the RDA for dietary Vitamin C is 90 mg for males and 75 mg for females older than 19 years (Institute of Medicine 2000).

C RDA

If you consume the RDA for Vitamin C, what plasma Vitamin C concentration will that yield? Shown below is how the plasma Vitamin C concentration varies according to ingested dose (Levine et al. 1996). Consuming the RDA value for Vitamin C  yields a plasma Vitamin C value of 20-30 uM. From the studies listed above, that would put you in the increased all-cause mortality risk group! How much dietary Vitamin C would be needed to achieve plasma values greater than 50 uM? From the plot, we see that a dietary Vitamin C intake at double the RDA would be necessary. Furthermore, because 2 studies have reported decreased all-cause mortality risk at plasma Vitamin C values greater than 66 uM, dietary intakes intake between 500-1000+ mg/day may be necessary:

C dose

Which foods are  Vitamin C-rich? As shown below, sweet peppers (yellow, red, and green) are the All-Stars for Vitamin C content per 100 calories:

C foods

What’s my average daily Vitamin C intake? Shown below is my average daily Vitamin C intake, 875 mg/day, separated by month. Based on that value, my plasma Vitamin C concentration should be ~ 70 uM, which may be associated with maximally reduced all-cause mortality risk.

C intake

With the goal of optimizing plasma Vitamin C, it is also important to monitor dietary sodium intake. Intestinal absorption of Vitamin C requires dietary sodium (Friedman and Zeidel 1999). As shown below, 1 ascorbate ion (asc-) is absorbed from the intestinal lumen into intestinal epithelial cells in the presence of 2 sodium (Na+) ions. Vitamin C can then diffuse into the blood as Asc- or as dehydroascorbate (DHA):

na asc transport

Accordingly, based on my average dietary Vitamin C intake of 875 mg/day, to maximize absorption, a corresponding dietary sodium intake of 1750 mg would also be necessary.

If you’re interested, please have a look at my book!

References

Bates CJ, Hamer M, Mishra GD. Redox-modulatory vitamins and minerals that prospectively predict mortality in older British people:the National Diet and Nutrition Survey of people aged 65 years and overBr J Nutr. 2011 Jan;105(1):123-32.

Fletcher AE, Breeze E, Shetty PS. Antioxidant vitamins and mortality in older persons: findings from the nutrition add-on study to the Medical Research Council Trial of Assessment and Management of Older People in the Community. Am J Clin Nutr. 2003 Nov;78(5):999-1010.

Friedman PA, Zeidel ML. Victory at C. Nat Med. 1999 Jun;5(6):620-1.

Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000.

Jia X, Aucott LS, McNeill G. Nutritional status and subsequent all-cause mortality in men and women aged 75 years or over living in the community. Br J Nutr. 2007 Sep;98(3):593-9.

Khaw KT, Bingham S, Welch A, Luben R, Wareham N, Oakes S, Day N. Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition. Lancet. 2001 Mar 3;357(9257):657-63.

Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR. Vitamin C pharmacokinetics in healthy volunteersevidence for a recommended dietary allowance. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3704-9.

Loria CM, Klag MJ, Caulfield LE, Whelton PK. Vitamin C status and mortality in US adults. Am J Clin Nutr. 2000 Jul;72(1):139-45.

Sahyoun NR, Jacques PF, Russell RM. Carotenoids, vitamins C and E, and mortality in an elderly population. Am J Epidemiol. 1996 Sep 1;144(5):501-11.

Simon JA, Hudes ES, Tice JA. Relation of serum ascorbic acid to mortality among US adults. J Am Coll Nutr. 2001 Jun;20(3):255-63.

Wang SM, Fan JH, Taylor PR, Lam TK, Dawsey SM, Qiao YL, Abnet CC.vAssociation of plasma vitamin C concentration to total and cause-specific mortality: a 16-year prospective study in ChinaJ Epidemiol Community Health. 2018 Dec;72(12):1076-1082.

Drink Green Tea, Reduce All-Cause Mortality Risk?

Is green tea consumption associated with reduced risk of death risk from all causes? To investigate this question, Tang et al. (2015) performed a meta-analysis of 5 studies, including 200,884 subjects. As shown below, drinking 5 cups (40 oz.) or less per day is associated with reduced all-cause mortality risk. Drinking 2-3 cups (16-24 oz.) of green tea per day was associated with maximally decreased all-cause mortality risk, ~10%.

green tea

If you’re interested, please have a look at my book!

Reference

Tang J, Zheng JS, Fang L, Jin Y, Cai W, Li D. Tea consumption and mortality of all cancers, CVD and all causes: a meta-analysis of eighteen prospective cohort studies. Br J Nutr. 2015 Jul 23:1-11.

Vitamin D: What’s an optimal daily intake and blood value?

How much Vitamin D is optimal for health? To answer this question, today I’ll examine the association between a circulating marker of Vitamin D, 25-hydroxyvitamin D, with all-cause mortality risk. Then, I’ll examine the literature to estimate a dietary intake that can achieve an optimal circulating 25-hydroxyvitamin D concentration.

Circulating 25-hydroxyvitamin D is the most commonly measured vitamin D metabolite because of its greater half life (~3 weeks) and up to 1000-fold higher serum levels compared with the physiologically active metabolite of vitamin D, 1,25-dihydroxyvitamin D (Zerwekh 2008). So what’s the evidence for the association between circulating 25-hydroxyvitamin D with all-cause mortality risk?

In a meta-analysis of 95 studies including 880,201 subjects, circulating 25-hydroxyvitamin D levels greater than 30 ng/mL (75 nmol/L) are associated with significantly reduced risk of death from all causes when compared with values less than 30 (<10, 20-29; Chowdhury et al. 2014):

d mort

Does the meta-analysis data for 25-hydroxyvitamin D mean that any values higher than 30 ng/mL are optimal for health? Maybe not. As shown below, although data from 11,315 subjects in the NHANES III study suggests that values between 30-40 ng/mL (75-99 nmol/L) may be optimal for decreased all-cause mortality risk (Sempos et al. 2013), 25-hydroxyvitamin D values greater than 48 ng/mL (120+ nmol/L) were associated with an increased all-cause mortality risk. Interestingly, in agreement with the Chowdhury meta-analysis data, this graph shows also increased mortality risk at values less than 30-40 ng/mL (75-99 nmol/L):

d mortality

However, whether increased circulating 25-hydroxyvitamin D is associated with increased all-cause mortality risk is debatable. In another meta-analysis (Garland et al. 2014), although circulating 25-hydroxyvitamin D values less than 30 ng/mL were again associated with increased risk, in contrast,  values greater than 48 ng/mL were not. Interestingly, values as high as 70 ng/mL (175 nmoL) were not associated with increased risk, either:

D UPDATED META

Aside from our skin making Vitamin D from sunlight during the summer months, what dietary intake can achieve the seemingly optimal 30-40 ng/mL (75-99 nmol/L) concentration for 25-hydroxyvitamin D in the winter? The RDA for Vitamin D is 600 IU for everyone older than 1 but younger than 70 (Institute of Medicine, 2010). If you’re over 70, the RDA is 800 IU. My average dietary intake is only ~170 IU-how can I increase this to at least the RDA, to achieve circulating values between 75-99 nmol/L?

Decent dietary sources of vitamin D include fish: salmon, sardines, mackerel, and tuna. Based on the table below (Holick 2007), eating ~3.5 ounces of wild salmon every day would achieve the RDA for vitamin D intake. In contrast, my daily tin of sardines puts me ~300 IU away from the RDA value! I could double my fish intake to ~8 oz./day, but I’d like to limit my animal protein intake, and, the extra ~200 calories would limit other nutrients that I’d like to enrich in my diet, like fiber.

d

Are there other, less calorie dense dietary sources of vitamin D? It’s important to note that dietary vitamin D can be found in 2 forms, D3, which is shown above, and D2. Which foods are rich in vitamin D2? Shown below is a picture of the best plant-based source of vitamin D2, maitake mushrooms:

maitake

The Vitamin D2 content of maitake mushrooms is 36 IU/calorie, whereas wild salmon only has 3.2 IU of vitamin D per calorie! Other “exotic” mushrooms (anything other than white button mushrooms is exotic to me!) like Chanterelle and Morel contain decent amounts of vitamin D2:

mush

Before adding maitake and other “exotic” mushrooms into my nutritional plan for their vitamin D content, it’s important to ask, “does D2 increase circulating 25-hydroxyvitamin D to an equal extent as D3”? Unfortunately, the answer is no: although D2 and D3 both increase circulating 25-hydroxyvitamin D levels, D2-based sources increase 25-hydroxyvitamin D level about half as effectively as D3 (Trang et al. 1998). So, instead of consuming ~35g of maitake mushrooms to add 400 IU of vitamin D into my diet (to achieve the RDA of 600 IU), I’ve added ~70g/day.

12/29/2015 Update: Because of Maitake’s relatively high cost, $5 for only 100g, and the burden of having to eat it every day, for the past ~3 months I switched to Vitamin D supplements to achieve a D intake of ~1100 IU/day. Blood testing showed that this intake yielded a circulating 25-hydroxyvitamin D winter concentration of 31 ng/mL, putting me at low risk for all cause mortality, based on the meta-analysis D data.

8/23/2016 Update: I stopped supplementing with 1000 IU of Vitamin D in June 2016, to explore the effect of 3-4 hours of weekly sun exposure on my circulating Vitamin D levels. My unsupplemented, circulating 25-hydroxyvitamin D level was 41 ng/mL in my 8/2016 blood test. Accordingly, I intend on increasing my  Vitamin D intake to 1600 IU (1400 supplemental, ~200 dietary)/day to achieve a circulating winter 25-hydroxyvitamin D level that is similar my  the summer value.

11/12/2017 Update: I’ve been supplementing with 2000 IU of D3/day, bringing my average daily total to ~2200 IU/day. Based on that, my latest circulating 25-hydroxyvitamin D level (tested in October, 2017) was 39 ng/mL .

If you’re interested, please have a look at my book!

References

Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC, Khan H, Baena CP, Prabhakaran D, Hoshen MB, Feldman BS, Pan A, Johnson L, Crowe F, Hu FB, Franco OH. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014 Apr 1;348:g1903.

Garland CF, Kim JJ, Mohr SB, Gorham ED, Grant WB, Giovannucci EL, Baggerly L, Hofflich H, Ramsdell JW, Zeng K, Heaney RP. Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D. Am J Public Health. 2014 Aug;104(8):e43-50.

Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81.

Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.

Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B, Yetley EA, Looker AC, Schleicher RL, Cao G, Burt V, Kramer H, Bailey RL, Dwyer JT, Zhang X, Gahche J, Coates PM, Picciano MF. Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES. J Clin Endocrinol Metab. 2013 Jul;98(7):3001-9.

Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2Am J Clin Nutr. 1998 Oct;68(4):854-8.

Zerwekh JE. Blood biomarkers of vitamin D status. Am J Clin Nutr 2008;87:1087S-91S.