In an earlier post I wrote about the association between elevated circulating levels of homocysteine with an increased risk of death from all causes (https://michaellustgarten.com/2017/11/22/homocysteine-and-all-cause-mortality-risk/). I started posted updates in that link, but I’ve decided to move them to this post. Plus, there’s new data (3/20/2018 measurement)!
12/5/2017: Despite 42 days of 800 micrograms of supplemental folic acid, bringing my average daily folate intake to 2026 micrograms/day, my plasma homocysteine was essentially unchanged at 11.7 uMoL, when compared with my baseline value of 11.8 uMol.What’s next on the list to reduce it? Trimethylglycine, also known as betaine. I’m a proponent of using diet as a first strategy, and to increase my dietary betaine levels, I’ll eat beets and quinoa, bringing my daily betaine levels to ~500 mg/day. Let’s see how it turns out on my next blood test!
1/2/2018: ~500 mg/day of betaine from beets and quinoa did absolutely nothing to my homecysteine levels. In fact, it got worse (15.3 uMoL)! To test the hypothesis that it wasn’t enough betaine, next I tried 4 grams/day of betaine (also known as trimethylglycine, TMG).
2/20/18: Supplemental TMG did absolutely nothing in terms of reducing my homocysteine to values below baseline! Also note that there is evidence that TMG increases blood lipids, including LDL and triglycerides (TG; Olthof et al. 2005), and that’s exactly what it did to me. My average LDL and TG values since 2015 (11 measurements) are 77 and 50 mg/dL, respectively. On TMG, these values increased to 92 and 72 mg/dL, respectively, making them my highest values over 11 individual blood tests (with the exception of 1 day with an LDL of 93 mg/dL). Next, I tried a stack that included 50 mg of B6, 1000 mcg of B12, and 400 mcg of methylfolate, as supplementation with these B-vitamins has been shown to lower homocystine (Lewerin et al. 2003).
3/20/18: Finally, some progress! My homocysteine levels were finally reduced during the B-vitamin supplementation period. I’ve written it like that because I’m not sure if it was the B-vitamins that caused it. For example, in the image below, we see the correlation between my dietary B6 intake with homocysteine. The trendline is down, which I would expect if B6 supplementation actually is playing a role in reducing my homocysteine levels. However, note that the correlation between my dietary B6 levels with homocysteine is not very strong (r = .48), resulting in a moderate R2 of 0.23 (similar data was obtained for B12 and folate). With 5 blood test measurements corresponding to 5 dietary periods, if B6 is playing a role, I would expect a stronger correlation. Nonetheless, with more data, the correlation may strengthen, so stay tuned for that!
If you’re interested, please have a look at my book:
Lewerin C, Nilsson-Ehle H, Matousek M, Lindstedt G, Steen B. Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial.vEur J Clin Nutr. 2003 Nov;57(11):1426-36.
Olthof MR, van Vliet T, Verhoef P, Zock PL, Katan MB. Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans. PLoS Med. 2005 May;2(5):e135.
Paper #1: Here I propose that the poor muscle composition (muscle that has fat in it) found in older adults may be related to an increased systemic microbial burden:
Paper #2: In this review, we discuss the emerging gut-muscle axis:
If you’re interested, please have a look at my book:
On a recent blood test, my plasma level of homocysteine (Hcy) was 11.9 uMol. Is that optimal minimizing disease risk and maximizing longevity? Let’s have a look at the literature.
A 2017 meta-analysis of 11 studies including 27,737 participants showed an increased risk of death from all causes (“all-cause mortality”; ACM) as circulating levels of homocysteine increase (Fan et al. 2017):
When looking at meta-analyses, it’s important to examine each of the individual studies. Here are the data for the 11 included studies:
- Kark et al. 1999: 1,788 older adults, average age 65y, followed for 9-11 years. Compared with values less than 8.5 uMol, subjects with elevated homocysteine (> 14.7) had a 2-fold higher risk of death from all causes.
- Bostom et al. 1999: 1,933older adults, verage age, 70y, median follow-up, 10y. Subjects with values > 14.3 uMol had 2-fold ACM risk, when compared with < 14.3.
- Hoogeveen et al. 2000: 811 older adults (average age, 65y), 5 yr follow-up. Non- diabetics had a 34% increased ACM risk (p=0.08), but diabetics had 2.5-fold increased ACM risk after a 5-yr follow-up.
- Vollset et al. 2001: 4,766 older adults (age range, 65-67y at study entry), median 4 yr follow-up. Compared with 5.1-8.9 uMol, values greater than 12 were significantly associated with a 2.4-4.5 increased ACM risk.
- Acevedo et al. 2003. 3,427 subjects, average age 56y, ~3yr follow-up. ACM risk lowest for < 9.4 uMol, compared with > 14.4.
- González et al. 2007: 215 older adults (average age, 75y), median 4 yr follow-up. Compared with < 8.7 uMol, values > 16.7 had 2.3-fold increased ACM risk.
- Dangour et al. 2008: 853 older adults (average age, 79y), ~7.6y follow-up. Homocysteins > 19.4 uMol associated with ~2-fold higher ACM risk, when compared with < 9.8.
- Xiu et al. 2012: 1,412 older adults (average age, ~75y), up to 10 year follow-up. 1.8-fold higher ACM risk comparing those with >14.5 uMol with < 9.3.
- Waśkiewicz et al. 2012: 7,165 middle aged adults, ~5yr follow- up. 1.8-fold increased ACM risk for subjects with homocysteine > 10.5 uMol(average age, 52y) when compared with < 8.2 (avg age, 40y).
- Wong et al. 2013: 4,248 older men, average age ~77y, ~5yr follow-up. 1.5-fold increased ACM risk for homocysteine values > 15 uMol.
- Swart et al. 2012: 1,117 older adults (average age, 75y), up to a 7yr follow-up. In 543 men, homocysteine was not associated with ACM risk. In 574 women, 1.7 to 1.9-fold higher ACM risk when comparing > 12.7 and >15.6 vs < 10.3 uMol.
Not included in their analysis:
- Petersen et al. 2016: 670 subjects, average age 65y, average follow-up 14.5y. Subjects with homocysteine values ≥ 10.8 μmol/l had a significant higher incidence of all-cause mortality:
In sum, the evidence appears consistent across these 12 studies that elevated homocysteine is associated with an increased risk of death from all causes. Based on the Fan et al. (2016) meta-analysis, lower appears better, with values < 5 uMol associated with maximally reduced ACM risk. Also based on that data, my ACM risk is ~1.5-fold increased!
To see how dietary changes and supplements have impacted my homocysteine levels, see this link: https://michaellustgarten.com/2018/03/23/reducing-homocysteine-updates/
If you’re interested, please have a look at my book:
Bostom AG, Silbershatz H, Rosenberg IH, Selhub J, D’Agostino RB, Wolf PA, Jacques PF, Wilson PW. Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med. 1999 May 24;159(10):1077-80.
Dangour AD, Breeze E, Clarke R, Shetty PS, Uauy R, Fletcher AE. Plasma homocysteine, but not folate or vitamin B-12, predicts mortalityin older people in the United Kingdom. J Nutr. 2008 Jun;138(6):1121-8.
Fan R, Zhang A, Zhong F. Association between Homocysteine Levels and All-cause Mortality: A Dose-Response Meta-Analysis of Prospective Studies. Sci Rep. 2017 Jul 6;7(1):4769.
González S, Huerta JM, Fernández S, Patterson AM, Lasheras C. Homocysteine increases the risk of mortality in elderly individuals. Br J Nutr. 2007 Jun;97(6):1138-43.
Hoogeveen EK, Kostense PJ, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes : 5-year follow-up of the Hoorn Study. Circulation. 2000 Apr 4;101(13):1506-11.
Kark JD, Selhub J, Adler B, Gofin J, Abramson JH, Friedman G, Rosenberg IH. Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem. Ann Intern Med. 1999 Sep 7;131(5):321-30.
Petersen JF, Larsen BS, Sabbah M, Nielsen OW, Kumarathurai P, Sajadieh A. Long-term prognostic significance of homocysteine in middle-aged and elderly. Biomarkers. 2016 Sep;21(6):490-6.
Swart KM, van Schoor NM, Blom HJ, Smulders YM, Lips P. Homocysteine and the risk of nursing home admission and mortality in older persons. Eur J Clin Nutr. 2012 Feb;66(2):188-95.
Waśkiewicz A, Sygnowska E, Broda G. Homocysteine concentration and the risk of death in the adult Polish population. Kardiol Pol. 2012;70(9):897-902.
Wong YY, Almeida OP, McCaul KA, Yeap BB, Hankey GJ, Flicker L. Homocysteine, frailty, and all-cause mortality in older men: the health in men study. J Gerontol A Biol Sci Med Sci. 2013 May;68(5):590-8.
Vollset SE, Refsum H, Tverdal A, Nygård O, Nordrehaug JE, Tell GS, Ueland PM. Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study. Am J Clin Nutr. 2001 Jul;74(1):130-6.
Yesterday the Sixers lost to the Warriors, despite being up 22 at the half.
Superficially, Joel Embiid had a solid game, with 21 points and 8 rebounds. As the Sixers crushed the Warriors in the 1st half, Embiid looked great in all aspects of the game: scoring (15 pts, 5-10 FG), rebounding (5), and ball movement. Early in the 3rd quarter, he dove for a ball and spent a quick minute on the floor looking exhausted. Maybe that’s why he was largely absent in the 2nd half despite playing 17 minutes-he only took 6 shots, and scored 6 points with 3 rebounds. This coincided with the Warriors going off in the 3rd and 4th quarter, pulling out the win.
So the big question is, would the outcome of this game been different had Embiid’s conditioning been better?
I have several thoughts about mlb.com’s Orioles article: (http://m.mlb.com/news/article/262168388/orioles-seeking-starting-pitching-for-2018/)
Yes, Schoop was an All-Star in 2017, and he deserved it. But note that he was a career .268 hitter in the minors, and even with his outstanding year in 2017, his MLB BA is .264. Based on his own data, Schoop had an above-average year. Note that in the minors, he followed a solid year in 2011 (.290 BA) with a .245 BA. I’m not saying that he’ll hit .245 next year, but I wouldn’t be surprised to see something closer to the .260-.270 range, as he’s averaged that throughout his minors+majors career.
Now onto the pitching. Yes, Cobb and Lynn are upgrades over Miley, Jimenez, Tillman, and potentially Hellickson, who didn’t have a good 2017. However, Gausman and Bundy have outstanding issues that should be discussed. Yes, Gausman throws hard, but is he good at getting outs? Between 2016-2017, he was average (WHIP = 1.26 in 2016), and below average (1.49 in 2017) at allowing hitters to reach base. However, the bright light for Gausman is that he was above-average (1.20 WHIP) after the All-Star break last year, but can he continue that in 2018? In terms of Bundy, last year he threw a career high for innings, 169.2. His biggest question for 2018 is whether he can remain injury-free and be stretched to 200 IP, as he’s averaged only 75 IP over 5 seasons.
On Friday, Kentavious Caldwell-Pope started a skirmish between the Suns and Lakers. Lonzo Ball, instead of getting involved, walked towards the bench and away from the pushing. He claimed that he didn’t want to get a technical foul, but isn’t it also possible that he didn’t want to get involved because of some issue with Pope? I’ve noticed a general disinterest towards Pope when both Ball and Pope are on the floor. Considering that Pope is a free agent at the end of the year, isn’t it possible that Ball is looking forward to Pope’s exit, for whatever reason?
Watch the video, see for yourself:
Yesterday, mlb.com released its “Who will be the top 10 prospects a year from now” list. First, it’s important to define some criteria. To be considered as a “prospect”, the player must not have played in MLB. With that in mind, at best, I agree with only 2 of the 10 players on Callis’ list (Guerrero and Bichette), which is shown below, and with the highest level reached for each player in 2017 in parenthesis:
- Vladimir Guerrero Jr. (A+): Guerrero had a great year in combined low A and A+: 0.323 BA, 13 HRs, 76 RBIs in 119 games, with more walks than strikeouts. Defensively, he was solid, with only 15 errors. Many players his age commit double the amount of errors from the left side of the infield (see Bichette, Rodgers, below).
- Gleyber Torres (AAA): Gleyber missed most of 2017 with Tommy John surgery, and there’s no way I’d pick a player coming off a major injury as a top-10 prospect for the following year.
- Luis Robert (Rookie level): It’s difficult to make accurate predictions on players like Robert, who have a small sample size: 28 career games at the rookie-ball level.
- Bo Bichette Jr. (A+): Like his teammate with the Blue Jays, Vlad Jr., Bichette had a monster year between combined low A and A+: 0.362 BA, 13 HRs, 74 RBIs in 110 games. In low A, Bichette flirted with hitting 0.400 for much of his 70 games prior to his call-up to A+. In contrast, he struggled at bit towards the end of the season, batting only 0.250 over the last 21 games. In terms of defense, Bichette made 21 errors in 86 games at SS, which projects to 40 errors over a full 162 game season, and is way too much. While Bichette’s offensive capability may be hard to match, I’d like to see how he handles AA-level pitching, and improve his defensive skills.
- Fernando Tatis Jr. (AA): Superficially, Tatis had a strong year: 0.275 BA, 22 HRs, 75 RBIs, 32 steals between low A and AA (14 games). But of concern is Tatis’ ability to make contact: he’s K’d 198 times in 186 games throughout his minor league career. Considering the struggle of players like Yoan Moncada with similarly high minor league strikeout rates in adjusting to MLB pitching, Tatis may have a tougher time handling higher-level pitching. Also, his defense has much room for improvement, with 45 errors at SS in 154 games.
- Brendan Rodgers (AA): Brendan Rodgers began the year at high-A on fire, batting 0.387 with 12 HRs and 47 RBIs in 51 games. He cooled a bit after being promoted to AA, and missed some time to injury. Similar to Bichette and Tatis, Rodgers has been error prone at SS, with 45 errors in 165 career games. Also, assuming a great year at AA/AAA for Rodgers in 2018, where will be play? The Rockies have Arenado at 3B, Story at SS, and LeMahieu at 2B, effectively blocking Rodgers’ promotion.
- MacKenzie Gore (Rookie level): Gore’s performance in the Rookie league was dominant, with a 1.27 ERA, 0.98 WHIP, and 34 K’s with only 7 BBs in 21 IP. However, many prospects have dominated Rookie ball only to fizzle in the upper levels. Again, this is too small of a sample size for me to make a prediction.
- Hunter Greene (Rookie level): #2 overall 2017 pick Hunter Greene did not fare well in his 7 games as a hitter (0.233 BA) or in his 3 games as a pitcher (12.46 ERA). While Greene will probably develop into a top-notch player, predictions about his 2018 production are difficult based on his small 2017 sample size. Also, when considering many MLB teams limit their pitcher’s IP (especially for newly drafted high school players) in the first 2 years post-draft, I don’t expect Greene to pitch more than 100 IP in 2018.
- Forrest Whitley (AA): Whitley was the 17th overall pick in the 2016 draft. As I mentioned earlier, many MLB teams start their newly-drafted high school pitchers out slow, with IP limits in their first couple of years. This is true for Whitley, who is being used as a starter, but threw 19 IP post-draft in 2016, and 92 IP in 2017. Whether Whitley can be stretched to 140+ in 2018 is unknown. Moreover, his relatively high BB rate in 2016 (more than 3 per 9 IP) makes me wonder how dominant he’ll be against upper level hitting. For ex., pitchers like Tyler Glasnow can dominate the minor leagues with high BB-rates, but struggle against more selective MLB hitters.
- Juan Soto (A-): Soto’s career stats are outstanding, with a 0.362 BA, 8 HRs, 50 RBIs, and great plate discipline (29 BBs, 38Ks) over 83 games. However, whether he can replicate his performance for a full 135 game minor league season and at higher minor league levels is unknown.
In contrast to the many lower-level players on mlb.com’s list, I prefer to identify prospects who have demonstrated above-average success at levels higher than Rookie-level ball. So which players are on my top 10 prospect list for 2018? Interestingly, I expect that 7 or 8 (or more) will make their MLB debut in 2018!
- Vladimir Guerrero Jr. (A+): Vlad Jr.s inclusion on my list is a no-brainer. Power, RBIs, high batting average and OBA, plate discipline (high BBs, low Ks), and solid defense collectively put him #1.
- Triston McKenzie (A+): The Indians have 3 players on my list (McKenzie, Bieber, Civale), and could’ve had 4, as Francisco Mejia was called up from AA-a scary thought considering they’re already playoff bound. McKenzie may be the most dominant pitcher in all of minor league baseball. He went 12-6 with a 3.46 ERA, 1.05 WHIP, and 186 Ks (45 BBs) in 143 IP. The question is, however, can he throw 150 IP+ again, as he broke 100 IP for the first time since being drafted in 2015, and keep the BB-rate low as he ascends to AA and beyond?
- Mike Soroka (AA): Forget about Newcomb and Sims, Braves fans, Mike Soroka will probably be your #1 pitcher very soon! Soroka was also drafted in 2015, and in 2017 went 11-8 with a 2.75 ERA, a 1.09 WHIP, and 125 K’s (34 BBs), in 153 IP. The ability of a young pitcher to consistently throw more than 140 IP in the minors should allow them to reach 200 IP relatively quickly in the majors, and he’s already thrown more than 140 IP twice. I expect Soroka to be in Atlanta’s rotation sometime in 2018. Interestingly, Soroka’s team was not very good, as it only won 58 games (80 losses), but yet Soroka still had a winning record.
- Shane Bieber (AA): Speaking about innings eaters, Shane Bieber, drafted in 2016 by the Indians threw 173 IP in 2017, and 159 IP in 2016, when combining his college and minors stats. In 2017, Bieber was 11-5 with a 2.86 ERA, a 1.13 WHIP, 162 K’s and only walked 10 hitters all year! Assuming he pitches well at AAA, Bieber can easily make the jump to 200 IP as a MLB starter.
- Aaron Civale (A+): The 3rd Indians starter on my prospect list is Aaron Civale. Drafted in 2016, Civale is also an innings eater with great control, throwing 164 IP and walking only 14, and was 13-6 with a 3.28 ERA, a 1.06 WHIP, and 142 K’s in 2017. This was the 2nd time Civale has thrown more than 150 IP, as he threw 152 IP in 2016, when combining his college and minors stats.
- Alex Wells (A-): My prospect theme of throwing a low of innings with great control continues with Alex Wells, who signed in 2016 after going undrafted. In his first full year in the minors, he threw 140 IP, going 11-5 with a 2.38 ERA, a 0.91 WHIP, 122 K’s and only 10 BBs. Whether Wells can break 140 IP again going forward is unknown, so let’s see how he does in 2018.
- Yohnny Chirinos (AAA): Perhaps the closest of the prospects on my list to reaching MLB is Chirinos, who has dominated throughout his minors career: 36-17, 2.75 ERA, 1.08 WHIP, 363 K’s and only 74 BBs in 474 career minors innings. In 2016, he threw 128 IP, and 168 IP in 2017, making a jump to 200+ likely next year with the Rays. In fact, I’m surprised they haven’t called him up already!
- Tom Eschelman (AAA): Probably the 2nd closest to reaching the majors is Eschelman, but it may be a while, considering how long it took the Phillies to call up Hoskins. Including his college stats, Eshelman has averaged 132 IP per year for the past 5 years, making it likely for him to be easily stretched out to reach high IP in the majors. In terms of production, in 2017, in 121 IP Eshelman was 10-3 with a 2.23 ERA, 0.94 WHIP, 80 K’s and only 13 BBs. I’d be shocked if Eshelman doesn’t make the Phillies starting rotation out of spring training in 2018.
- Eloy Jiminez (AA): Eloy Jiminez was traded by the Cubs to the White Sox for Jose Quintana and is a player who potentially has the best power/RBI potential in the minors. Based on data for 300 minor league games, Jiminez has averaged 23 HRs and 111 RBIs, when projected over a full 162 game season. And don’t worry, he won’t strike out like Gallo or Judge-his 0.302 career BA and 4.75 Abs per K suggest otherwise. The issue with Jiminez is his health, missing 20 and ~40 games in 2016 and 2017, respectively.
- Jon Duplantier (A+): Last, but not least, is Jon Duplantier, the Diamondbacks 3rd round pick in 2016. In 2017, Duplantier’s 1st full minor league season, he went 12-3 with a 1.39 ERA, a 0.98 WHIP, and 165 K’s (42 BBs) in 136 IP. In Duplantier’s last college season, he threw 111 IP and had a relatively high walk rate, 3.81. So the issues for him going forward are, can he break 150 IP, and, keep the BB-rate low as he ascends?
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!
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!
If you’re interested, please have a look at my book!