11 epigenetic clocks have been published since 2011, but which is best for predicting aging and age-related disease? In this video, I present findings from a recent publication, “Underlying features of epigenetic aging clocks in vitro and in vivo”, that compared data for 11 epigenetic clocks, and derived a new epigenetic clock, the meta-clock.
Platelets are one of the 19 variables that are included in the biological age calculator, aging.ai. The reference range is 150-400 platelets per nanoliter (*10^9/L), but within that range, what’s optimal?
In a study of 21,635 adults older than 35y (average age wasn’t reported), platelets between 230-270 were associated with a maximally reduced risk of death from all causes (Bonaccio et al. 2016):
Similarly, in a study of 21,252 adults (average age 53y), values ~250 were associated with maximally reduced risk of death from all causes Vinholt et al. (2017) :
What about in older adults? In a study of 159,746 postmenopausal women (average age, 63y), maximally reduced risk of death from all causes was associated with platelet values between 200-256 (Kabat et al. 2017).
In a smaller study (36,262 older adults, average age, 71y), platelet values ~250 were associated with maximally reduced risk for all-cause mortality. Interestingly, even at platelet values ~250, mortality risk was highest for non-Hispanic whites, when compared with lower mortality risk for non-Hispanic blacks and Hispanics (Msaouel et al. 2014):
In 5,766 older adults (average age, 73y), platelets higher than 200-300 was associated with an increased risk of death from all causes (van der Bom et al 2009). Risk for values between 100-199 was not different when compared against 200-299, but there was a non-significant trend towards increased risk (1.05, 95% CI: 0.97, 1.14).
In 131,308 older adults (~73y), maximally reduced risk of death from all causes was associated with platelet values between 200-300, whereas risk significantly increased below and above that range, respectively Tsai et al. (2015):
In sum, the data suggests that platelet values ~250 may be optimal for heath, with 200-300 as the “optimal range” within the 150-400 reference range. What are my values? Over the past 16 years, I’ve measured my platelets 25 times, and 6x, my platelets were below this 200-300 range. I’m not too worried about it, though, as most of my measurements are within that range!
Are there any variables that are correlated with platelets? For me, the strongest correlation over 18 tracked blood tests from 2015 – 2019 is my body weight. As my weight increases, my platelets are higher (r = 0.64, p-value = 0.006). Platelets have been reported to increase in association with elevated inflammation (CRP; Izzi et al. 2018), but I only have 3 co-measurements for CRP with platelets. I have a blood test scheduled for next week, more data coming soon!
If you’re interested, please have a look at my book!
References
Bonaccio M, Di Castelnuovo A, Costanzo S, De Curtis A, Donati MB, Cerletti C, de Gaetano G, Iacoviello L; MOLI-SANI Investigators. Age-sex-specific ranges of platelet count and all-cause mortality: prospective findings from the MOLI-SANI study. Blood. 2016 Mar 24;127(12):1614-6.
Izzi B, Bonaccio M, de Gaetano G, Cerletti C. Learning by counting blood platelets in population studies: survey and perspective a long way after Bizzozero. J Thromb Haemost. 2018 Sep;16(9):1711-1721. doi: 10.1111/jth.14202.
Kabat GC, Kim MY, Verma AK, Manson JE, Lin J, Lessin L, Wassertheil-Smoller S, Rohan TE. Platelet count and total and cause-specific mortality in the Women’s Health Initiative. Ann Epidemiol. 2017 Apr;27(4):274-280.
Msaouel P, Lam AP, Gundabolu K, Chrysofakis G, Yu Y, Mantzaris I, Friedman E, Verma A. Abnormal platelet count is an independent predictor of mortality in the elderly and is influenced by ethnicity. Haematologica. 2014 May;99(5):930-6.
Tsai MT, Chen YT, Lin CH, Huang TP, Tarng DC; Taiwan Geriatric Kidney Disease Research Group. U-shaped mortality curve associated with platelet count among older people: a community-based cohort study. Blood. 2015 Sep 24;126(13):1633-5.
Vinholt PJ, Hvas AM, Frederiksen H, Bathum L, Jørgensen MK, Nybo M. Thromb Res.Platelet count is associated with cardiovascular disease, cancer and mortality: A population-based cohort study. 2016 Dec;148:136-142.
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 2-3 cups (16-24 oz.) of green tea per day was associated with maximally decreased all-cause mortality risk, ~10%.
Post update (9/15/2019): Is there new data since this post was first published (2015) for the association between green tea with all-cause mortality risk? Two relatively large studies have been published since then. First, in a study of 164,681 men (average age, ~53y), consuming green tea (~15g/day) was associated with a maximally reduced risk of death from all causes (black lines; Liu et al. 2016). However, note that this data included both smokers and non-smokers. For non-smokers (green lines), all-cause mortality risk was maximally reduced even further at smaller doses, including ~ 6-10g of green tea/day:
In support of these data, never-smoking men and women (average age, ~52y) that drank more than 8.2g, and 3.3g, respectively, of green tea had an 11% reduced risk of all-cause mortality in Zhao et al. (2017).
The data is clear, drink green tea!
If you’re interested, please have a look at my book!
Reference
Liu J, Liu S, Zhou H, Hanson T, Yang L, Chen Z, Zhou M. Association of green tea consumption with mortality from all-cause, cardiovascular disease and cancer in a Chinese cohort of 165,000 adult men. Eur J Epidemiol. 2016 Sep;31(9):853-65.
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.
Zhao LG, Li HL, Sun JW, Yang Y, Ma X, Shu XO, Zheng W, Xiang YB. Green tea consumption and cause-specific mortality: Results from two prospective cohort studies in China. J Epidemiol. 2017 Jan;27(1):36-41.
Have you had a blood test and aren’t sure what values for platelets may be optimal for health? The reference range is 150-400 platelets per nanoliter (*10^9/L). Within that range, what’s optimal?
In a study of 21,635 adults older than 35y (average age wasn’t reported) with a 7.6-year follow-up, platelets between 230-270 was associated with maximally reduced risk of death from all causes (Bonaccio et al. 2016):
In a study of 21, 252 adults (average age 53y) with an average follow-up of 3.5y, values ~250 were associated with maximally reduced risk of death from all causes Vinholt et al. (2017) :
What about in older adults? In a study of 159, 746 postmenopausal women (average age, 63y) with a 16-year follow up, maximally reduced risk of death from all causes was associated with platelet values between 200-256 (Kabat et al. 2017).
In a study of 36, 262 older adults (average age, 71y) with an 11-year follow-up, platelet values ~250 were associated with maximally reduced risk for all-cause mortality. Interestingly, even at platelet values ~250, mortality risk was highest for non-Hispanic whites, when compared with non-Hispanic blacks and Hispanics (Msaouel et al. 2014):
In 5,766 older adults (average age, 73y) that were followed for 12-15 years, values higher than 200-300 had an increased risk of death from all causes (van der Bom et al 2009). Risk for values between 100-199 was not different when compared against 200-299, but there was a non-significant trend towards increased risk (1.05, 95% CI: 0.97, 1.14).
In 131,308 older adults (~73y) with a 6-yr follow-up, maximally reduced risk of death from all causes was associated with values between 200-300, whereas risk significantly increased below and above that range, respectively Tsai et al. (2015):
In sum, the data suggests that platelet values ~250 may be optimal for heath, with 200-300 as the “optimal range” within the 150-400 reference range. What are your values?
If you’re interested, please have a look at my book!
References
Bonaccio M, Di Castelnuovo A, Costanzo S, De Curtis A, Donati MB, Cerletti C, de Gaetano G, Iacoviello L; MOLI-SANI Investigators. Age-sex-specific ranges of platelet count and all-cause mortality: prospective findings from the MOLI-SANI study. Blood. 2016 Mar 24;127(12):1614-6.
Kabat GC, Kim MY, Verma AK, Manson JE, Lin J, Lessin L, Wassertheil-Smoller S, Rohan TE. Platelet count and total and cause-specific mortality in the Women’sHealth Initiative. Ann Epidemiol. 2017 Apr;27(4):274-280.
Msaouel P, Lam AP, Gundabolu K, Chrysofakis G, Yu Y, Mantzaris I, Friedman E, Verma A. Abnormal platelet count is an independent predictor of mortality in the elderly and is influenced by ethnicity. Haematologica. 2014 May;99(5):930-6.
Tsai MT, Chen YT, Lin CH, Huang TP, Tarng DC; Taiwan Geriatric Kidney Disease Research Group. U-shaped mortality curve associated with platelet count among older people: a community-based cohort study. Blood. 2015 Sep 24;126(13):1633-5.
van der Bom JG, Heckbert SR, Lumley T, Holmes CE, Cushman M, Folsom AR, Rosendaal FR, Psaty BM. Platelet count and the risk for thrombosis and death in the elderly. J Thromb Haemost. 2009 Mar;7(3):399-405.
Vinholt PJ, Hvas AM, Frederiksen H, Bathum L, Jørgensen MK, Nybo M. Thromb Res.Platelet count is associated with cardiovascular disease, cancer and mortality: A population-based cohort study. 2016 Dec;148:136-142.
If you’re interested, please have a look at my book!
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%.
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.
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):
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):
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:
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.
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:
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:
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 D2. Am 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.
In an earlier article I wrote about how cooking foods at a high temperature (greater than 250ºF, including frying, baking, roasting and grilling) produces the neurotoxic and carcinogenic compound, acrylamide (http://voices.yahoo.com/acrylamide-chocolate-another-10217911.html?cat=5). However, the adverse effects acrylamide that I discussed were solely based on rodent studies. In this follow-up article, I’ll comprehensively discuss the evidence relating dietary acrylamide with human cancer.
Before introducing the data, it’s important to note that dietary acrylamide intake in all of the studies discussed below were calculated based on food frequency questionnaires. The highest acrylamide consuming group was approximately 40 µg/day, in comparison with low consumers of dietary acrylamide, ~10 µg /day. Without a doubt these values for dietary acrylamide intake are underestimated-for example, 1 ounce of Pringles potato chips contains 70 µg of acrylamide, and the commonly thought of as “healthier chips”, Baked Lays has 31µg/ounce (1 bag of chips).
Breast Cancer
Six large epidemiological studies (ranging from 33,000-120,000 subjects) and 1 smaller study (1500-6000 subjects) investigated the association between dietary acrylamide and breast cancer risk. Of these, 1 study, the UK Women’s Cohort Study identified a 20% significantly increased risk between acrylamide intake and premenopausal breast cancer (Burley et al. 2011). The other six studies did not show an association between acrylamide intake and breast cancer risk (Pellucchi et al. 2006, Hogervorst et al. 2007, Pedersen et al. 2009, Larsson et al. 2009, Wilson et al. 2009, Wilson et al. 2010).
Endometrial Cancer
Three large epidemiological studies have investigated the association between dietary acrylamide and endometrial cancer. In two of these studies, risk of cancer was increased by 41% and 99%, respectively (Wilson et al. 2010, Hogervorst et al. 2007). No association between dietary acrylamide intake and risk of endometrial cancer was found in the Swedish Mammography Study (Larsson et al. 2009).
Ovarian Cancer
No association between dietary acrylamide and risk of ovarian cancer was found in the small- scale Italian Cohort study, or, in 2 large-scale epidemiological studies (Pellucchi et al. 2006, Larsson et al. 2009, Wilson et al. 2010). However, a 122% increased risk for ovarian cancer in non-smokers was found in the Netherlands Cohort Study on Diet and Cancer (Hogervorst et al. 2007).
Prostate, Pancreatic, Brain Cancer
Five separate studies found no association between dietary acrylamide and risk of prostate cancer (Pellucchi et al. 2006, Hogervorst et al. 2008, Wilson et al. 2009, Larsson et al. 2009, Wilson et al. 2012). Similarly, pancreatic cancer risk is not increased (Pelucchi et al. 2011, Hogervorst et al. 2008), nor is brain cancer (Hogervorst et al. 2009), or, thyroid cancer (Schouten et al. 2009).
Esophageal cancer
One small study (987 subjects) found a 23% increased risk for esophageal cancer, and an 88% increased risk in those with a BMI greater than 25. In two other studies (Pellucchi et al. 2006, Hogervorst et al. 2008), no association between dietary acrylamide and esophageal cancer was found.
Head-neck cancer
Increased risk for oral-cavity cancer in female non-smokers in a large study (121,000 subjects; Schouten et al. 2009) was found. No association for oral cavity, pharynx or larynx cancer in a smaller study (1500-6000 subjects; Pellucchi et al. 2006)
Kidney Cancer
Although risk of kidney cancer was significantly increased by 59%, it appears as if this data was skewed by smokers. In non-smokers, risk of kidney cancer was not significant (Pellucchi et al. 2006). No association between dietary acrylamide and risk of kidney cancer was also identified in three additional studies (Mucci et al. 2003, Mucci et al. 2004, Pellucchi et al. 2007).
Gastric, Colon, Rectal cancer
A small study with 1129 subjects found a 40% decreased risk of large bowel cancer (Mucci et al. 2003). Four studies have not found a similar association (Pellucchi et al. 2006, Mucci et al. 2006, Hogervorst et al. 2008, Larsson et al. 2009).
Lung Cancer
A 55% decreased risk of lung cancer, in women was identified by Hogervorst et al. (2009).
Bladder cancer
Significant only in smokers, as 15+ cigarettes/day significantly increased risk of bladder cancer in those with the highest dietary acrylamide intake, relative to the lowest intake (Hogervorst et al. 2008).
Blood cancer
Multiple myeloma and follicular myeloma were found to be significantly increased by 14% and 28% for every 10 µg increment in dietary acrylamide (Bongers et al. 2012).
Conclusions
The easy interpretation of scientific studies is that if six studies show no effect and one study shows a positive effect, that the no effect-data is the real answer. For example, in the case of breast cancer, six studies showed no effect, whereas one study showed a significant association between acrylamide and premenopausal breast cancer. Should we conclude that there is no risk for breast cancer? As I mentioned earlier, it is likely that total dietary acrylamide intake was underestimated, and therefore, it is my opinion that none of the 25 studies should have shown an association between acrylamide and cancer. Therefore, that there was indeed a significant association for breast cancer with potentially underestimated acrylamide values is significant. Also, dietary acrylamide was shown to be significantly associated with myeloma, head-neck cancer, esophageal cancer, endometrial cancer and ovarian cancer. Paradoxically, dietary acrylamide reduced risk of lung and large bowel cancer.
What should someone who is interested in optimal health do with this information? Knowing that dietary acrylamide is indeed significantly associated with increased risk of human cancers, I would reduce or eliminate cooking food at a high temperature. I have!
If you’re interested, please have a look at my book!
References:
Bongers ML, Hogervorst JG, Schouten LJ, Goldbohm RA, Schouten HC, van den Brandt PA. Dietary acrylamide intake and the risk of lymphatic malignancies: the Netherlands Cohort Study on diet and cancer. PLoS One. 2012;7(6):e38016.
Burley VJ, Greenwood DC, Hepworth SJ, Fraser LK, de Kok TM, van Breda SG, Kyrtopoulos SA, Botsivali M, Kleinjans J, McKinney PA, Cade JE. Dietary acrylamide intake and risk of breast cancer in the UK women’s cohort. Br J Cancer. 2010 Nov 23;103(11):1749-54.
Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA. A prospective study of dietary acrylamide intake and the risk of endometrial, ovarian, and breast cancer. Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2304-13.
Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA. Dietary acrylamide intake and the risk of renal cell, bladder, and prostate cancer. Am J Clin Nutr. 2008 May;87(5):1428-38
Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA. Dietary acrylamide intake is not associated with gastrointestinal cancer risk. J Nutr. 2008 Nov;138(11):2229-36.
Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA. Lung cancer risk in relation to dietary acrylamide intake. J Natl Cancer Inst. 2009 May 6;101(9):651-62.
Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA. Dietary acrylamide intake and brain cancer risk. Cancer Epidemiol Biomarkers Prev. 2009 May;18(5):1663-6.
Larsson SC, Akesson A, Wolk A. Long-term dietary acrylamide intake and breast cancer risk in a prospective cohort of Swedish women. Am J Epidemiol. 2009 Feb 1;169(3):376-81.
Larsson SC, Håkansson N, Akesson A, Wolk A. Long-term dietary acrylamide intake and risk of endometrial cancer in a prospective cohort of Swedish women. Int J Cancer. 2009 Mar 1;124(5):1196-9.
Larsson SC, Akesson A, Bergkvist L, Wolk A. Dietary acrylamide intake and risk of colorectal cancer in a prospective cohort of men. Eur J Cancer. 2009 Mar;45(4):513-6.
Larsson SC, Akesson A, Wolk A. Long-term dietary acrylamide intake and risk of epithelial ovarian cancer in a prospective cohort of Swedish women. Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):994-7.
Larsson SC, Akesson A, Wolk A. Dietary acrylamide intake and prostate cancer risk in a prospective cohort of Swedish men. Cancer Epidemiol Biomarkers Prev. 2009 Jun;18(6):1939-41.
Lin Y, Lagergren J, Lu Y. Dietary acrylamide intake and risk of esophageal cancer in a population-based case-control study in Sweden. Int J Cancer. 2011 Feb 1;128(3):676-81.
Mucci LA, Dickman PW, Steineck G, Adami HO, Augustsson K. Dietary acrylamide and cancer of the large bowel, kidney, and bladder: absence of an association in a population-based study in Sweden. Br J Cancer. 2003 Jan 13;88(1):84-9.
Mucci LA, Lindblad P, Steineck G, Adami HO. Dietary acrylamide and risk of renal cell cancer. Int J Cancer. 2004 May 1;109(5):774-6.
Mucci LA, Adami HO, Wolk A. Prospective study of dietary acrylamide and risk of colorectal cancer among women. Int J Cancer. 2006 Jan 1;118(1):169-73.
Pedersen GS, Hogervorst JG, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA. Dietary acrylamide intake and estrogen and progesterone receptor-defined postmenopausal breast cancer risk. Breast Cancer Res Treat. 2010 Jul;122(1):199-210.
Pelucchi C, Galeone C, Levi F, Negri E, Franceschi S, Talamini R, Bosetti C, Giacosa A, La Vecchia C. Dietary acrylamide and human cancer. Int J Cancer. 2006 Jan 15;118(2):467-71.
Pelucchi C, Galeone C, Dal Maso L, Talamini R, Montella M, Ramazzotti V, Negri E, Franceschi S, La Vecchia C. Dietary acrylamide and renal cell cancer. Int J Cancer. 2007 Mar 15;120(6):1376-7.
Pelucchi C, Galeone C, Talamini R, Negri E, Polesel J, Serraino D, La Vecchia C. Dietary acrylamide and pancreatic cancer risk in an Italian case–control study. Ann Oncol. 2011 Aug;22(8):1910-5.
Schouten LJ, Hogervorst JG, Konings EJ, Goldbohm RA, van den Brandt PA. Dietary acrylamide intake and the risk of head-neck and thyroid cancers: results from the Netherlands Cohort Study. Am J Epidemiol. 2009 Oct 1;170(7):873-84.
Wilson KM, Mucci LA, Cho E, Hunter DJ, Chen WY, Willett WC. Dietary acrylamide intake and risk of premenopausal breast cancer. Am J Epidemiol. 2009 Apr 15;169(8):954-61.
Wilson KM, Bälter K, Adami HO, Grönberg H, Vikström AC, Paulsson B, Törnqvist M, Mucci LA. Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study. Int J Cancer. 2009 May 15;124(10):2384-90.
Wilson KM, Mucci LA, Rosner BA, Willett WC. A prospective study on dietary acrylamide intake and the risk for breast, endometrial, and ovarian cancers. Cancer Epidemiol Biomarkers Prev. 2010 Oct;19(10):2503-15.
Wilson KM, Giovannucci E, Stampfer MJ, Mucci LA. Dietary acrylamide and risk of prostate cancer. Int J Cancer. 2012 Jul 15;131(2):479-87.
The main drawback to optimal health if you eat store-bought chocolate is that cacao beans are roasted, thereby increasing the concentration of the carcinogen, acrylamide (https://atomic-temporary-71218033.wpcomstaging.com/2014/07/27/acrylamide-is-in-chocolate-another-reason-why-cooking-food-at-high-temperature-is-not-good-for-you/). Besides eating homemade chocolate made from raw cacao beans (https://atomic-temporary-71218033.wpcomstaging.com/2014/09/21/homemade-chocolate-in-2-minutes/), are there any health benefits to drinking raw cacao?
The answer is yes, and it comes from the Kuna Indians, who live on a group of islands near Panama. The Kuna have been shown to have a low average blood pressure (BP, 110/70 mm Hg), and, do not experience the age-related increase in blood pressure that is common in Western society (Hollenberg et al. 1997). More importantly, death rates from cardiovascular disease and cancer, the #1 and #2 causes of death in the US were almost completely eliminated in the Kuna. Between 2000 to 2004, on the mainland of Panama, Bayard et al. (2007) reported that for every 100,000 residents, 83 died from cardiovascular disease (CVD), and 68 died from cancer. In contrast, per 100,000 Kuna, these death rates were reduced to 9 for CVD (a 9-fold reduction!) and 4 (a 15-fold reduction!) for cancer, respectively. In other words, cardiovascular disease and cancer are almost non-existent as a cause of death among the Kuna!
One could make the argument that the Kuna have decreased rates of CVD and cancer if it can be shown that their population is younger than on mainland Panama. The incidence of CVD and cancer increase with age, so if the Kuna population was younger than on the mainland, this could possibly explain their reduced death rates. However, the opposite was found to be true: approximately 94% of the residents of Panama are younger than 55 years of age, whereas ~87% of the Kuna are younger than 55. In addition, ~6% of Kuna’s population were found between the age of 55-64; ~4.4% were 65-74, and, ~2.4% were older than 75. In contrast, only 3% of mainland Panamanians were 55-64, ~1.9% were 65-74, and ~1.1% were older than 75 (Bayard et al. 2007). In other words, the percentage of Kuna older than 55 years was more than doubled, relative to mainland Panama! Not only do the Kuna have less CVD and cancer, they live longer than their mainland counterparts.
Before discussing how this is possible, it’s important to mention that the Kuna’s salt intake has been reported to be higher than both mainland Panama and, when compared with a Western diet. The Kuna eat, on average, 5500 mg of salt per day (Hollenberg et. al 1997). In comparison, Kuna who migrate to mainland Panama consume ~3300 mg/day (McCullough et. al 2006), subjects on a Western diet consume ~3700 mg, and, vegans consume ~1400 mg salt/day (Fontana et. al 2007). In other words, the Kuna eat more salt, but yet have lower BP, the absence of an age-related rise in BP, and have reduced risk of disease and mortality, relative to their Westernized-diet counterparts on the mainland of Panama.
Do the Kuna have genes that protect them from elevated blood pressure? If the Kuna were genetically protected, one would anticipate that they could move to an urban environment and maintain low blood pressure. However, Kuna that migrated to mainland Panama approximately 20 years earlier were found to have an increased incidence of both hypertension, and an age-related rise in BP (Hollenberg et. al 1997). This indicates that the Kuna were not protected by genes, and the factor that was keeping their blood pressure down was environmental.
So, how is this possible? There may be clues in the Kuna diet, which is almost exclusively plant and fish based, with almost no dairy, meat or nuts. The Kuna eat more fruit, 5 servings/day, vs. 1 serving/day on the mainland. The Kuna eat approximately 6 oz. fish/day, compared with, 1.5 oz/ day on the mainland (McCullough et. al 2006). Both increased fruit and fish intake may be responsible for the improved health that the Kuna experience, relative to their mainland counterparts.
But, there is another factor which is dramatically different in the Kuna diet when compared to the mainland-the Kuna consume more than 4 cups, or 30-40 ounces of a cocoa drink on a daily basis. Mainland Panamanians ingest little cocoa, and what they take is commercially available and flavanol-poor (McCullough et. al 2006). In contrast, unlike almost all commercially available chocolate, the cocoa consumed by the Kuna is not roasted. To make their cocoa drink, the Kuna grind raw cacao beans, which is then boiled with banana. After boiling this mixture, it is poured through a strainer, leaving behind the cocoa and banana solids. Because it’s not roasted, Kuna cocoa contains all of the health benefits of the cacao bean, with none of the acrylamide!
It’s important to note that the cocoa ingested by the Kuna is naturally very rich in a specific subclass of flavonoids known as flavanols, including epicatechin, catechin, and flavanol-based oligomers known as procyanidins (Chevaux et. al 2001, Fisher and Hollenberg 2005). Kuna cocoa beans provide 3000 mg/100g flavanols. Kuna cocoa powder provides less (flavanols are lost during the fermentation process), at ~2000 mg/100g cocoa. In contrast, 6 commercially available cocoa powders /cocoa drinks didn’t exceed 150 mg flavanols/100g cocoa (Fisher and Hollenberg 2005). High levels of flavanol have been shown to reduce risk of death from coronary artery disease by as much as 58% (Mukamal et al. 2002).
Since I don’t live with the Kuna off the mainland of Panama, I don’t have access to unfermented cacao beans. However, raw, organic, fermented, non-roasted cacao beans are indeed available online. To make the cocoa drink, I use 1 oz. of cacao beans, 1 medium-large banana and ~35 oz. of water, boiled for 10-15 minutes. Then, I pass this solution through a strainer, and drink it once it cools down. It’s delicious!
If you’re interested in watching an ABC news video on the Kuna and the preparation of this cocoa drink, here is the link:http://abcnews.go.com/Health/video/cocoa-kuna-indians-panama-native-americans-chocolate-production-13402637.
If you’re interested, please have a look at my book!
References:
Acrylamide data via: http://www.fda.gov/Food/FoodborneIllnessContaminants/ChemicalContaminants/ucm053549.htm
Bayard V, Chamorro F, Motta J, Hollenberg NK. Does flavanol intake influence mortality from nitric oxide-dependent processes? Ischemic heart disease, stroke, diabetes mellitus, and cancer in Panama. Int J Med Sci. 2007 Jan 27;4(1):53-8.
Chevaux KA, Jackson L, Villar ME, et al. Proximate mineral and procyandin content of certain foods and beverages consumed by Kuna Amerinds of Panama. J Food Composit Anal. 2001;14: 553–563.
Fisher NDL, Hollenberg NKH. Flavanols for cardiovascular health: the science behind the sweetness. J Hypertension. 2005;23: 1453–1459.
Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk. Rejuvenation Res. 2007 Jun;10(2):225-34.
Hollenberg NK, Martinez G, McCullough M, et al. Aging, acculturation, salt intake, and hypertension. Hypertension. 1997; 29:171–176.
McCullough ML, Chevaux K, Jackson L, Preston M, Martinez G, Schmitz HH, Coletti C, Campos H, Hollenberg NK. Hypertension, the Kuna, and the epidemiology of flavanols. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S103-9; discussion 119-21.
Mukamal KJ, Maclure M, Muller JE, Sherwood JB, Mittleman MA. Tea consumption and mortality after acute myocardial infarction. Circulation 2002; 105:2476–2481.
http://www.nal.usda.gov/fnic/foodcomp/Data/Flav/Flav02-1.pdf
Michael Lustgarten 