Monthly Archives: November 2015

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 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).


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.


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.

An evidence-based approach for minimizing tooth decay risk

I’d like to keep my teeth healthy for as long as possible. I brush my teeth in the morning and at night, and floss every night, because daily flossing is associated with reduced mortality risk ( Is there anything else that I can do to optimize my oral health? To answer that question, it’s important to know how tooth decay (also known as caries) occurs. As shown below, bacteria located on our teeth (in plaque) use dietary sugars to make acid, which demineralizes tooth enamel, thereby resulting in caries (Limeback et al. 2012).

caries overview

Not all dietary sugars are equal in their ability to produce tooth decay. In the picture below, sugars with red boxes are the most cariogenic. For example, the worst offenders in terms of tooth decay are sucrose and glucose. Also note that starch is cariogenic, but less when compared with sucrose and glucose. The least cariogenic sugars are sorbitol and mannitol, and, the sugar xylitol has been shown to be protective against tooth decay (Limeback et al. 2012).

sugars cario

After eating a high sugar meal, there is an oral bacteria-induced increase in acidity that can lead to tooth demineralization. At an oral plaque pH of 5.5, tooth enamel demineralization occurs (Stephan and Miller 1943). Shown below is a graph of plaque pH vs. time for the 60 minutes following an oral glucose rinse. The green line is indicative of someone who is caries resistant: their plaque pH decreases from ~6.8 to ~5.8, followed by a relatively quick return to the starting pH value after 60 minutes. Note that at no point does the green line drop below the 5.5 threshold for enamel demineralization to occurr. The yellow line is indicative of someone at moderate tooth decay risk: their plaque pH drops from 6.8 to below 5.5, where it remains for ~ 10 minutes, and then slowly returns to baseline pH values after 60 minutes. The red line is indcative of someone that is at high risk for tooth decay: after the glucose rinse at time 0, their plaque pH rapidly drops below 5.5 and remains there for ~50 minutes, where significant teeth demineralization may occur. Note that their plaque pH doesn’t return to the baseline pH value after 60 minutes, either.

plaque ph

With these data in mind and my goal to reduce tooth decay risk I bought pH strips to test my daily oral pH. Shown below is what the pH strip looks like, without having been dipped in my saliva. Adjacent to that is the pH color scale, and to the right, my average daily fasted oral pH, ~6.5:

no samp20151015_110200pH4hr 20151015_130558

The good news is that I’ve yet to see an oral pH value below 6.5, which puts me at low risk for tooth decay. To further minimize that risk, in addition to brushing and flossing, after meals and throughout the day I gargle with a homemade 1% sodium bicarbonate (physiological saline is ~0.9%) and 10% xylitol solution. I use sodium bicarbonate to temporarily neutralize any potential oral acids. Xylitol can protect against tooth decay by reducing plaque and the level of tooth decay-causing bacteria (i.e. Streptococci mutans) in saliva and plaque (Söderling 2009). For example, fluoride-containing toothpaste in the presence of 10% xylitol reduces tooth decay more than fluoride toothpaste alone (Sintes et al. 1995; Sintes et al. 2002). However, it’s important to note that some xylitol-based studies have not been shown to reduce tooth decay risk (Riley et al. 2015). At worst, including xylitol may have no effect, whereas at best it may reduce oral Streptococci mutans, thereby decreasing tooth decay risk. 

After gargling, my normal oral ph (~6.5) changes to alkaline (~8.5), as shown in the pH strip below:


Couldn’t I use a store-bought mouthwash instead?  The measured pH of several commercially available mouthwashes is shown in the table below (Sun et al. 2014). Note that some are below the critical pH for tooth demineralization, 5.5! Others aren’t too far away from 5.5, either. In contrast, the pH of my homemade mouthwash pH is ~8.0.

mwash pH


Limeback H et alComprehensive Preventive Dentistry, Chapter 1: “A brief introduction to oral diseases: caries, periodontal disease, and oral cancer”. page 1-24. July 2012. ISBN: 978-0-8138-2168-9.

Riley P, Moore D, Ahmed F, Sharif MO, Worthington HV. Xylitol-containing products for preventing dental caries in children and adultsCochrane Database Syst Rev. 2015 Mar 26;3:CD010743.

Sintes JL, Escalante C, Stewart B, McCool JJ, Garcia L, Volpe AR, Triol C. (1995). Enhanced anticaries efficacy of a 0.243% sodium fluoride/10% xylitol/silica dentifrice: 3-year clinical results. American Journal of Dentistry, 8, 231–235.

Sintes JL, Elías-Boneta A, Stewart B, Volpe AR, Lovett J. (2002). Anticaries efficacy of a sodium monofluorophosphate dentifrice containing xylitol in a dicalcium phosphate dihydrate base. A 30-month caries clinical study in Costa Rica. American Journal of Dentistry, 15, 215–219.

Söderling EM. (2009) Xylitol, mutans streptococci, and dental plaque. Advances in Dental Research, 21, 74–78.

Stephan RM and Miller BF. (1943) A Quantitative Method for Evaluating Physical and Chemical Agents which Modify Production of Acid in Bacterial Plaques on Human Teeth. Journal of Dental Research, 22, 45–51.

Sun FC, Engelman EE, McGuire JA, Kosmoski G, Carratello L, Ricci-Nittel D, Zhang JZ, Schemehorn BR, Gambogi RJ. Impact of an anticaries mouthrinse on in vitro remineralization and microbial control. Int J Dent. 2014;2014:982071.