Vitamin C For Runners

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Vitamin C may be an important supplement for runners. A runner's quads lengthen to slow their body's descent on landing, a type of eccentric exercise. This eccentric stress not only causes Delayed Onset Muscle Soreness (DOMS), but it also causes immediate weakness. If you've ever had problems descending stairs after a marathon, you've had DOMS. The good news is that experiencing DOMS provides a protection from future bouts, something known as the Repeated Bout Effect (RBE), which is where Vitamin C comes in. As well as being an antioxidant, Vitamin C is important in may other ways, including the production of the scaffolding that makes up muscles (collagen.) There is some evidence that Vitamin C may help with the RBE, and without sufficient Vitamin C, the ability to adapt to long runs may be impaired. While Vitamin C has been shown to interfere with the way people adapt to exercise at a biochemical level, that doesn't appear to translate into practical problems. If you take Vitamin C as a supplement, it's probably best to take it spread evenly through the day rather than a single larger dose, and the dose should be built up slowly as it can cause stomach upsets and diarrhea. It's unclear to me if the research indicates there is an increased risk of kidney stones from Vitamin C.

1 The Role of Vitamin C

Vitamin C is best known for its role as an antioxidant. However, it's not only an antioxidant, but it's also cofactor for 15 different enzymes[1], including the production of norepinephrine[2], carnitine[3], and collagen[4]. It also enhances non-heme iron absorption[5]. Increased Vitamin C may also boost the amount of Collagen synthesized[6][7]. This is especially valuable for runners, as collagen is a key structural protein, including muscle fibers[8] and tendons[9]. Even within the role as an antioxidant there is the possibility that different antioxidants may fulfill different roles. For instance, there is evidence that Vitamin C depleted plasma is susceptible to fat (lipid) oxidation, even when other anti-oxidants are present[10]. Personally, I suspect that these various roles may result in differing actions of vitamins C in differing circumstances. Vitamin C is concentrated in nearly all cells in the body above plasma levels, such as the brain with 16-18x and muscle with 4-6x, though It's unclear why many tissues concentrate Vitamin C levels well beyond the level needed for the enzymatic actions, sometimes 10-100x higher[11]. There is evidence from animal models that the Vitamin C needs may vary widely, possibly due to genetic differences[12]. This has been seen in humans, where there is wide variation in susceptibility to scurvy amongst sailors[12].

2 Vitamin C Requirements

The recommended intake for vitamins C is focused on preventing deficiency problems, primarily scurvy[13]. Vitamin C deficiency (scurvy) results in lassitude (fatigue), coiled hair, gum problems, anemia, hemorrhages, tooth loss and other problems[11]. Sometimes the only symptom of vitamins C deficiency is lassitude, even when plasma levels are below 8 uM[14]. Most animals can produce their own Vitamin C, except for humans and other primates, Guinea pigs, fruit bats, and some birds and fish[11]. The optimum dose of Vitamin C for runners is unclear based on the available research.

3 Vitamin C Intakes

Vitamin C is absorbed in the small intestine, reaching peak plasma levels in 2-3 hours, and then to extracellular fluids[11]. Over many days, the level of vitamin C in the plasma stabilizes, as shown below[14]]].

The fasting plasma Vitamin C levels of a subject given 60mg/day[14].

/ Varying doses increase the plasma levels with diminishing returns[14], giving a sigmoid (s) shaped curve. Plasma Vitamin C levels are well regulated, with even extreme oral doses (3g every 4 hours) results in peak levels of only 220 mmol/L[15][16] (note that IV Vitamin C produces vastly higher plasma levels.) /

The stable fasting plasma Vitamin C levels reached with varying doses[14]

The graphs above are from a single dose, with the measurement in the fasting state, but it's only at low doses of Vitamin C that peak and fasting levels are the same (i.e. 15 mg twice a day is 8.7 mmol/L) [11]. If you look at the graph below you can see that the time course of Vitamin C and the timing of the doses results in different areas under the curve[16]. Here you can see that while the higher doses of Vitamin C result in similar levels after 20+ hours, the levels following the doses are quite different and much higher for higher doses. Taking Vitamin C regularly though the day would result in higher average levels than a single dose. For instance, 1g/day of Vitamin C is sufficient to saturate fasting plasma levels, but levels may transiently raise higher (250+ mmol/L)[17].

Dose response over the course of a day to different doses of Vitamin C[16]

./ One study found that taking 60mg/day took ~3 weeks to reach stable plateau blood levels, and there were sharp change in blood levels up to 100mg, then far less change from 200mg up to 2,500mg[14].

4 Factors Influencing Vitamin C Needs

Both smoking and diabetes decrease Vitamin C plasma levels compared with controls, increasing intake needs[11]. Vitamin C can be reversibly or irreversibly oxidized, with irreversible oxidation consuming Vitamin C, resulting in an increased dietary need[11].

5 Distribution of Vitamin C

Vitamin C is regulated by controlling absorption in the intestine, and the balance of excretion/reabsorption in the kidney[18], as well as by recycling Vitamin C after it has functioned as an antioxidant[19]. Typically, humans only have about 1,500mg of Vitamin C in their body[20]. Because vitamin C is an anion at physiologic pH, it cannot simply diffuse across the cell membrane to extracellular fluid and must be actively transported[21], which results in different tissues having different concentrations as shown in the picture below[11]. While the level of vitamin C in skeletal muscle is lower than many other tissues[22], the size of the muscles suggests they main contain 66% of the body's vitamin C[23]. A study of Vitamin C from Kiwi fruit found for intakes between ~50-210mg/day, there was a strong correlation between plasma and muscle Vitamin C levels[24]. /

The distribution of Vitamin C at 100 mg/day[11].

6 Vitamin C, Exercise, and Aerobic Capacity

There is lots of evidence that Vitamin C changes how the human body responds to exercise, but interpreting the evidence is not straightforward. Many of the studies have found changes in enzyme levels after exercise with Vitamin C compared with placebos, but don't measure exercise outcomes such as V̇O2max[25]. I've mostly ignored these studies as they may not reflect real world impacts. In fact, one study of 54 recreationally endurance-trained individuals taking either 100mg Vitamin C plus 235 mg Vitamin E or a placebo found that cellular adaptation to exercise was hampered by the supplements, but no changes in V̇O2max or running performance[26]. I've included the studies I've found where the outcomes are measured in real world terms for aerobic capacity (primarily V̇O2max.)

  • There's strong evidence that Vitamin C deficiency results in impaired exercise ability[27][28][29]. The remainder of the studies in this section will look at Vitamin C supplementation at doses beyond those needed for the prevention of clinical deficiency.
  • Many studies do not have controls with standardized Vitamin C levels, and at low intake levels small changes in intake make a large difference in plasma levels. Interventions should have controls with low intakes of Vitamin C, as some studies have used controls where the plasma levels of Vitamin C are already near saturation[11]. For instance, in one study the Vitamin C treated group had similar plasma levels to the placebo group, rendering the identical results between the groups a bit meaningless[30] (at least they measured.)
  • 15 amateur athletes split between placebo and 90 days of 500mg Vitamin E, 30mg beta-carotene, and then 1,000mg Vitamin C for the last 15 days[31]. There was no measurement of the Vitamin C status in the subjects. The V̇O2max was 57 for the placebo group and 60 for the supplemented. The increase in V̇O2max was not significant for either group, but workload at 4 mmol/L of Lactate was higher in the supplemented group than the placebo (but not at 2 mmol/L). I found this interesting, but inconclusive given the issues of measuring Lactate, and I'd interpret this as showing no impact of Vitamin C on fitness.
  • Of 14 Sedentary men (V̇O2max < 43), 5 were given 1g/day of Vitamin C while 9 acted as controls[32]. All underwent 8 weeks of training, 3 days/week for 40 minutes, ramping up from 65% to 80% of V̇O2max. There were no statistically different changes in V̇O2max, though the average improvement was 22% in the placebo and 10.8% in the supplemented group, mostly due to the lower initial V̇O2max in the placebo group. With such a small group, it's possible that a larger study would reveal differences or that the differences would disappear. Interestingly, they also studied rats and found that Vitamin C dramatically reduced their endurance improvement, though again no significant differences in the rats' V̇O2max. (The levels of Vitamin C in the supplemented group were ~165 mmol/L and in the control group were ~45 mmol/L.)
  • A study that used "antioxidant rich foods" during altitude training found that V̇O2max increased in both treated and control groups equally, but hemoglobin concentration increased more in the treated group[33].
  • A study of 15 recreationally active men were given 1g/day of Vitamin C (n=8) or a placebo for 4 weeks of high intensity interval training, with no difference in improvement for V̇O2max, 10K time trial, or running economy[34].
  • 21 active men underwent cycling training 5 days/week for 12 weeks while 11 of them received 500mg Vitamin C and 400 IU of Vitamin E[30]. There was no statistical difference in improvement in V̇O2max, maximum power, workload at Lactate Threshold, or muscle Glycogen content.

7 Vitamin C, Exercise, and Muscular Resiliency

Unlike cycling or swimming, running involves eccentric muscular stress, with the muscles extending under load to absorb the body weight on landing[35][36], something that's exacerbated by downhill running[37]. This eccentric stress is one of the causes of muscle soreness after a marathon[38]. This damage causes Delayed Onset Muscle Soreness (DOMS), and it's particularly important to runners because while the soreness is delayed, there is muscular weakness that occurs during the damaging exercise[39]. This means the soreness you experience after a marathon involves muscular weakness during the race. There are various ways of reducing the muscle damage and treating the soreness from DOMS, but the most important is called "the repeated bout effect" (RBE). The principle of RBE is that performing exercise that causes DOMS and recovering then gives protection from similar exercise in the future[40]. There are a number of possible mechanisms behind RBE[41], including neural adaptations, changes in muscle fiber structure, changes in inflammatory response, and extracellular matrix structural remodeling. It's the extracellular matrix structural remodeling that's of interest here, as that remodeling involves collagen formation[42], and as noted above, Vitamin C is an important part in collagen formation[6][7]. There's one study that suggests that Vitamin C might be important for the Repeated Bout Effect[43] . This study used 1,000mg of Vitamin C and 400 IU Vitamin E per day on 22 moderately trained men and subjected them to two bouts of downhill running (40 min, -10%, 65-70% V̇O2max.) They found that the supplementation not only reduced DOMS after the first bout, but enhanced the RBE. Obviously, this is only one study, it used Vitamin E in addition to Vitamin C, and didn't measure strength deficits, but it's highly suggestive.

7.1 My Vitamin C Experiment

The research above mirrors my personal anecdotal experience. I've been taking Vitamin C in doses around 1g/day for many years as it seems to help my skin condition. I stopped taking Vitamin C for some months in 2018 due to the research suggesting it interferes with enzyme response to exercise. During that time without Vitamin C supplementation, I was also trying to ramp back up my Downhill Running via Treadmill Descents. I believe downhill running was a key component in my training for ultras, allowing me to race 100 miles with little muscle soreness the next day. Unfortunately, I found that 60-90 minutes of downhill running produced severe DOMS, and I couldn't get past that mark. I seemed to be stuck at that level and unable to make progress, where in previous years I'd been able to build up to marathon+ distance downhill runs. After a particularly disappointing all-day, self-supported run on Mount Mitchell in August I revisited the research on Vitamin C more comprehensively and found the study on Vitamin C and the Repeated Bout Effect. Having restarted my Vitamin C intake, and upped it to 500mg 3-5x per day, I found my ability to run downhill returned rapidly. I was able to built up to running marathon distance downhill runs at -10% within a few months, and only #1 on the DOMS scale. So for me at least, Vitamin C may be a critical component to endurance running.

7.2 Addition Eccentric Exercise Research

Sadly, most research on eccentric exercise has focused on preventing or treating causes Delayed Onset Muscle Soreness (DOMS), rather than maximizing the Repeated Bout Effect, or even limiting the immediate reduction on strength. For instance, a study showed that 3g/day of Vitamin C reduced DOMS, but not reduce muscular power[44].

8 Vitamin C and Tendons

A 2018 review of the research found that Vitamin C studies on animals improved tendon and bone healing, but that the human research at that point was limited[45]. One study found that 200 IU Vitamin E with 500 mg Vitamin C improved ACL healing (1-6 weeks) after ACL surgery, but the differences disappeared by 3 months[46].

9 Vitamin C, Running, and the Common Cold

Controlled studies suggest that Vitamin C may reduce the length of the common cold, but not prevent the colds except in those undergoing severe exercise such as a marathon[47].

10 Vitamin C and Diabetes

A full review of the research is outside the scope of this article, and further reading is encouraged. Recent reviews suggest that Vitamin C may help slow the progression of diabetes complications[48] as well as possibly reducing the risk of developing diabetes[49][50].

11 Vitamin C and Kidney Stones

There is conflicting evidence concerning Vitamin C and kidney stones, possibly because there are many things that change the risk for kidney stones. Personally, I feel that any risk for kidney stones from Vitamin C is offset by my physical activity, low body fat, good hydration, and high intakes of magnesium, potassium, and calcium. As always, read the research yourself and talk to your doctor if you have concerns.

A metabolite of Vitamin C is oxalate that is excreted in urine[51], and calcium oxalate is a common type of kidney stone[52]. Two studies found that 1,000mg of Vitamin C twice a day increased oxalate in the urine, a risk for kidney stones [53][54]. However, two other studies found that 4g/day[55] or 1, 5, 10g/day[56] didn't raise oxalate levels. One study found even found that 2g/day of Vitamin C as a supplement didn't change urine oxalate, but the same dose from Orange Juice did raise the urine oxalate[57].

Likewise, there are conflicting results from large scale prospective studies. A study of 48,850 men found that the risk of kidney stones was more than doubled with those that took more than 7 Vitamin C tablets per week[58]. The study doesn't have dosage information as it uses survey data that just ask for number of supplements taken. Another study of 45,619 men found that compared with those who consumed less than 90mg/day, 1+g/day had a 40% greater incidence of kidney stones, and even those that consume 90-249mg/day had 22% greater incidence[59]. This relationship between Vitamin C and kidney stones only emerged after adjusting for potassium intake. Potassium intake is associated with Vitamin C intake, and the risk of kidney stones goes down with potassium intake, so the two tend to "even out". This reflects the general complexity of nutrition and kidney stones, where many dietary factors may impact kidney stone formation. The contrasts with a study of 45,251 men[60] that found no relationship between Vitamin C intake and the incidence of kidney stones. (A study of 85,557 women[61] found no change in risk, but women seem to have a lower incidence of kidney stones.)

Kidney stone risk may be associated with various nutritional factors, possibly including things that might reduce the risk, such as calcium, potassium, magnesium, fluid intake[59]. Obesity may also increase the risk for kidney stones[62], with one estimate suggesting a 20% increase in risk for each 5 BMI and 12% for each 5Kg[63]. Diabetes may increase risk of kidney stones, while physical exercise may reduce the risk[63].

12 Vitamin C, Depression, and Anxiety

There is some evidence that Vitamin C may be related to depression and anxiety. More details to follow.

13 Vitamin C Conversion Factors

To convert ascorbic acid mg /100 mL to mol/L, multiply by 56.78[64]. (This will be of use if you're digging into the research papers.)

14 References

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