Keywords
fasting - thrombosis - venous thrombosis - dehydration - anticoagulation
Introduction
Intermittent fasting is becoming more popular as health benefits are described in
recent literature. Weight loss, reduction in abdominal fat, decrease inflammation,
lowering blood pressure, and reduction of insulin resistance are some of the observed
effects of dietary restriction.[1] Various forms of fasting exist but medical supervision is usually recommended, especially
when food restriction is more important or for a prolonged period of time.[2]
[3]
[4]
Water-only fasting is defined by restriction of every type of food (zero-calorie diet)
except water. In the 1960s and 1970s, fasting duration of 60 days and more was considered
for important weight loss, but this practice has been abandoned due to important complications
and deaths. At that time, fasts were improperly done due to lack of physicians' and
researchers' knowledge about safety and risks.[5] This kind of fast has also been described in nonobese persons for religious purposes.[6]
[7]
Nevertheless, potential health benefits are still reported after shorter course of
water-only fasting done under appropriate medical supervision.[4]
[8]
[9] However, safety of such food restriction is still not well established and relies
on limited data.[4]
[5]
We describe the case of a man who developed a right lower limb proximal deep vein
thrombosis (DVT) in the context of unsupervised water-only fasting.
Case Presentation
A 59-year-old male, with a body weight of 70 kg and body mass index of 24 kg/m2, presented with a progressive right lower limb pain and edema starting at the end
of a voluntary 2-week water-only fasting period. He was not known for any relevant
past medical or family history. In the last year, the patient had undergone three
medically unsupervised water-only fasting periods of 1 week for potential health benefits
purposes. He had progressively increased not only the frequency of these fasts but
also their duration up to 2 weeks. In his second 2-week fasting, the patient was still
walking 5 km per day, lost around 10 kg (14% of total body weight), and started drinking
500 mL of water per day only on day 6 (i.e., no water for the first 5 days). He did
not take any food supplements or weight loss drugs. The last 3 days of the fast (days
12 to 14), the patient reduced his activities and his walks because of fatigue but
he was not bedridden. While he was resuming food intake (only fruit juice), he developed
his right leg symptoms. Ten days after, he sought medical attention, and a diagnosis
of right lower limb proximal DVT (peroneal veins up to the common femoral vein) was
made. There were no identified risk factors for venous thromboembolism (VTE) (no recent
surgery, trauma or admission to hospital, no long travel, no family history of VTE,
no known comorbidities, no obesity, no active smoking, no varicose veins, no recent
coronavirus disease infection) and blood work was normal at diagnosis. Thrombophilia
testing was not done. Apixaban was initiated and the patient's symptoms progressively
improved over the next weeks. At 3 months, anticoagulation was discontinued, and a
repeated venous ultrasound revealed a residual thrombus without recanalization in
the peroneal and femoral veins, but popliteal vein was partially recanalized.
After 6 months of follow-up, he was still presenting slight right leg edema, heaviness
while walking, and new varicose veins, but did not have a venous thrombosis recurrence.
Discussion
Fasting Causes Dehydration
Complex physiologic processes occurring with fasting have been hypothetically suggested
as a cause of observed increased diuresis and potential resulting dehydration.[10] The decrease of glucose intake impairs sodium reabsorption as glucose-sodium cotransport
in renal proximal tubules is inhibited. This ensued natriuresis is not compensated
enough by the distal tubular sodium reuptake and then explains resulting osmotic diuresis
and subsequent dehydration.[10]
[11]
[12]
As the patient was taking no calorie and 500 mL of water per day starting only on
day 6, and experiencing a 10-kg weight loss in 14 days (weight that he regained in
1 week after restarting food intake), significant dehydration was most likely present.
Also, it is improbable that only the first 5 days with no intake (no food, no water)
explain the whole dehydration as weight loss was progressive over the 14 days. Despite
water intake, raised hematocrit and blood urea nitrogen were reported after water-only
fasting in two cases, reflecting potential dehydration.[7]
[13]
Dehydration is a Risk Factor of VTE
Dehydration is one of the potential explanations put forward to explain the increased
VTE incidence observed after prolonged travel.[14] This state likely results in hypercoagulability induced by hemoconcentration and
hyperviscosity as reflected in part by increased biochemical parameters such as hematocrit,
plasma proteins, plasma, and urine osmolality.[15] Other conditions in which VTE likely occurs because of dehydration have been described
such as following ischemic strokes, intense exercises, and gastroenteritis.[16]
[17]
[18]
[19]
[20] Also, according to some authors, seasonal variation of VTE incidence could hypothetically
be related to dehydration, occurring more often with higher temperature.[21]
Some literature suggests that theoretically, medically supervised water-only fasting
could in fact decrease thrombosis risk. Decreased platelet formation and activity
was observed, but this was tested only after 7 days of fasting.[9] Also, increased fibrinolytic activity was described in 12 healthy men after a 60-hour
fast in which only water was allowed.[22] However, vascular clinical outcomes under these circumstances were not reported.
Of note, these studies do not apply to our unsupervised patient after a 2-week fast.
Important dehydration in this healthy and active patient most likely led to a state
of hypercoagulability. It is unknown if an undiagnosed underlying predisposition to
thrombosis such as a hereditary thrombophilia was present or if fasting can affect
coagulability in another way. We believe that important dehydration in the context
of fasting can represent on its own a transient risk factor for VTE. However, it is
unknown if it should be interpreted as a major or minor one and deemed at low risk
of recurrence.[23] We have not found any previous report of thrombosis complications following fasting.[5]
[6]
Immobility could also represent a risk factor in fasting if the patient becomes confined
to bed because of weakness. However, we highly doubt it explains the VTE in our case.
Indeed, despite the reported reduction in his activities in the last 3 days of his
fast, the patient was still mobile.
A concerted decision was made to treat 3 months with anticoagulation, as recommended
with provoked VTE caused by a transient risk factor.[24] No recurrence was observed up to 3 months after stopping the treatment.
There are limitations to the present case, as exact hydration status was not established
at the time the DVT occurred considering the patient had regained his usual weight
at diagnosis. Also, we do not have any available blood test results at the end of
the 2-week fast in correlation with dehydration. This is only one case and firm conclusions
cannot be drawn.
Conclusion
While literature suggests potential benefits from intermittent fasting, the public
needs to be aware of the potential life-threatening complications associated with
important dehydration in the setting of medically unsupervised fasting, and these
might include VTE. Whether VTE caused in the context of dehydration as the only identified
risk factor should be approached as a low recurrence risk situation or not still needs
to be clarified.
